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KR20130129326A - Lytic bacteriophage specific for acinetobacter genus resistant to carbarpenem - Google Patents

Lytic bacteriophage specific for acinetobacter genus resistant to carbarpenem Download PDF

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KR20130129326A
KR20130129326A KR1020120053306A KR20120053306A KR20130129326A KR 20130129326 A KR20130129326 A KR 20130129326A KR 1020120053306 A KR1020120053306 A KR 1020120053306A KR 20120053306 A KR20120053306 A KR 20120053306A KR 20130129326 A KR20130129326 A KR 20130129326A
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용동은
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연세대학교 산학협력단
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Abstract

The present invention relates to a lytic bacteriophage specific to Acinetobacter genus, with resistance to carbapenem which is a strong antibiotic. A new method for proliferating bacteriophages using a liquid medium is used for sensitively detecting the lytic bacteriophages with apoptotic ability specific to carbapenem resistant Acinetobacter genus which is not detected by an existing method, thereby being used for the purpose of preventing and treating diseases caused by carbapenem resistant Acinetobacter.

Description

카바페넴 제제에 내성을 보이는 아시네토박터 균속을 용균하는 박테리오파아지 {ＬＹＴＩＣ ＢＡＣＴＥＲＩＯＰＨＡＧＥ ＳＰＥＣＩＦＩＣ ＦＯＲ ＡＣＩＮＥＴＯＢＡＣＴＥＲ ＧＥＮＵＳ ＲＥＳＩＳＴＡＮＴ ＴＯ ＣＡＲＢＡＲＰＥＮＥＭ}TECHNICAL FIELD The present invention relates to a bacteriophage which is resistant to carbapenem and which is resistant to Aspenbaum.

본 발명은 강력한 항균제인 카바페넴에 대한 내성을 보이는 아시네토박터 균속을 용균시키는 박테리오파아지에 관한 것이다. The present invention relates to a bacteriophage that lyses an Ashinobacterium sp. Which shows tolerance to carbapenem, a potent antimicrobial agent.

아시네토박터 균속은 그람음성 간균으로 포도당 비발효 세균이며, 이들은 토양, 물, 하수 등을 포함한 자연환경, 사람의 피부, 구강, 호흡기계 점막 등에 상재균으로 분포한다. 이들 세균은 신생아, 비장 절제술 시행 환자, 장기간 스테로이드를 투여한 환자, 항암 치료 중인 암환자, 장기 이식 환자, 집중치료실 환자와 같은 면역력이 저하된 고위험군에서 내인성 기회감염의 주요 원인균이다(Patrick PR, et al.eds. Manual of Clinical Microbiology. 8th eds. ASM press. 2003). 최근에는, 항생제 내성 세균이 점차 증가하고 있으며 가장 강력한 항균력을 보이는 항생제인 카바페넴 제제에도 내성을 보이는 아시네토박터 균주가 등장하였다. 90-60 rule에 의하면 감염증 환자를 감수성을 보이는 항균제를 이용하여 적절한 치료를 하는 경우 약 90%의 양호한 예후를 기대할 수 있고, 내성을 보이는 항균제로 치료하는 경우는 약 60% 밖에 반응하지 않았다 (Rex JH and Pfaller MA. Has antifungal susceptibility testing come of age? Clin Infect Dis. 2002; 15; 35(8):982). 이에 따라서, 다제내성 세균감염증 치료에 대한 대안 물질로써 기존의 화합요법제제를 보완할 수 있는 박테리오파아지에 대한 필요성이 대두하였다. Ashinotobacter spp. Is a gram-negative bacterium, which is non-fermenting bacteria of glucose, and it is distributed in the natural environment including soil, water, sewage, etc., as a fungus in human skin, oral cavity and respiratory mucous membrane. These bacteria are a major cause of endogenous opportunistic infections in immunocompromised high-risk groups such as neonates, spleen-treated patients, long-term steroid-treated patients, cancer patients undergoing chemotherapy, organ transplant patients, and intensive care unit patients (Patrick PR, et al. < RTI ID = 0.0 > 5. < / RTI > Recently, antibiotic-resistant bacteria are gradually increasing, and the strain of Ashinobacterium, which is also resistant to the carbapenem agent, has been introduced. According to the 90-60 rule, about 90% of patients with infectious disease susceptible to antibiotics are expected to have a good prognosis, while those treated with resistant antibiotics only respond to about 60% (Rex JH and Pfaller MA. Has antifungal susceptibility testing come of age? Clin Infect Dis. 2002; 15; 35 (8): 982). Therefore, there is a need for a bacteriophage that can complement existing combination therapies as an alternative to the treatment of multidrug-resistant bacterial infections.

항생제 내성 박테리아의 출현 이후 기존의 항생제 대체제로서의 관심으로부터 항균제로서의 박테리오파아지 사용이 하나의 가능성으로 제기되었다. 박테리오파아지는 생존을 위해 세균에 감염되어 그 세포 내에서만 증식하며, 박테리오파아지와 그 숙주 간의 관계는 높은 특이성을 갖는 것으로 알려져 있다. 세균을 감염시킬 때, 파아지는 용균성(Lytic) 또는 용원성(Lysogenic) 생활사를 따른다. 용균성 파아지는 숙주의 세포 기구들이 파아지 자신의 구조물들을 만들게 한 후 세포를 파괴하거나 용해시켜 새로운 파아지 입자들을 방출시킨다. 용원성 파아지는 자신의 핵산을 숙주세포의 염색체에 편입시켜 세포를 파괴하지 않고 세포와 함께 복제된다. 일정한 조건이 되면 용원성 파아지는 용균성으로 전환될 수 있다.Since the emergence of antibiotic resistant bacteria, the use of bacteriophage as an antimicrobial agent has emerged as a possibility from the interest as a conventional antibiotic substitute. Bacteriophages are infected by bacteria to survive and proliferate only within their cells, and the relationship between the bacteriophage and its host is known to have high specificity. When infecting bacteria, phages follow a lytic or lysogenic life cycle. The fungal phage allows host cell machinery to make its own structures and then destroys or dissolves the cells to release new phage particles. A phage phage incorporates its own nucleic acid into the chromosome of the host cell and replicates with the cell without destroying the cell. Under certain conditions, the phage can be converted to a fungus.

본 발명은 다제내성 세균감염증 치료의 대안 물질로 기존의 화학용법 제제를 보완할 수 있는 용균성 박테리오파아지를 기존과는 다른 방법으로 스크리닝하여 다제내성 아시네토박터 균속을 선택적으로 사멸시킬 수 있는 새로운 용균성 박테리오파아지를 분리하고, 분리된 박테리오파아지의 형태적 및 유전적 특성을 분석하여 이를 타 박테리오파아지와 구별하여 특징지을 수 있는 유전체의 유전자 서열을 비교하여 차별성을 확인한 후, 이러한 파아지를 포함하는 다제내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물을 개발하여 본 발명을 완성하였다. The present invention relates to a new method for screening a fungus bacteriophage capable of supplementing an existing chemical agent as an alternative agent for the treatment of multidrug-resistant microbial infections by selectively screening the multidrug-resistant strains of Asnertobacter, The morphological and genetic characteristics of the isolated bacteriophages were analyzed, and the genomic sequences of the genomes were identified by distinguishing them from other bacteriophages, and the discrimination was confirmed. The present invention has been accomplished by developing a pharmaceutical composition for the treatment of diseases caused by tolerance to asthma.

본 발명의 목적은 항생제 카바페넴 내성 아시네토박터 균속에 대한 특이적 감염 및 사멸능을 갖는 신규한 박테리오파아지 및 상기 박테리오파아지의 용균 효소를 제공하는 것이다.It is an object of the present invention to provide a novel bacteriophage having a specific infectious and killing activity against the antibiotic carbapenem-resistant Acinetobacter sp. And the lytic enzyme of the bacteriophage.

본 발명의 또 다른 목적은 카바페넴 내성 아시네토박터 균속에 대한 특이적 감염 및 사멸능을 갖는 신규한 박테리오파아지 및 이의 용균 효소를 이용하여 카바페넴 내성 아시네토박터 균속에 의해 유발되는 질환의 예방 및 치료용 조성물과 질환 개선용 식품 조성물을 제공하는 것이다. It is another object of the present invention to provide a novel bacteriophage having specific infectivity and killing activity against carbapenem-resistant Acinetobacter sp. And its lytic enzyme to prevent and prevent diseases caused by carbapenem-resistant Acinetobacter sp. And to provide a therapeutic composition and a food composition for improving disease.

하기 설명에서, 본 발명의 완전한 이해를 위해서, 다양한 특이적 상세사항, 예컨대, 특이적 형태, 조성물, 및 공정 등이 기재되어 있다. 그러나, 특정의 구체예는 이들 특이적 상세 사항 중 하나 이상 없이, 또는 다른 공지된 방법 및 형태와 함께 실행될 수 있다. 다른 예에서, 공지된 공정 및 제조 기술은 본 발명을 불필요하게 모호하게 하지 않게 하기 위해서, 특정의 상세사항으로 기재되지 않는다. "일 구체예" 또는 "구체예"에 대한 본 명세서 전체를 통한 참조는 구체예와 결부되어 기재된 특별한 특징, 형태, 조성 또는 특성이 본 발명의 하나 이상의 구체예에 포함됨을 의미한다. 따라서, 본 명세서 전체에 걸친 다양한 위치에서 표현 "한 가지 구체예에서" 또는 "구체예"의 상황은 반드시 본 발명의 동일한 구체예를 나타내지는 않는다. 추가로, 특별한 특징, 형태, 조성, 또는 특성은 하나 이상의 구체예에서 어떠한 적합한 방법으로 조합될 수 있다. In the following description, for purposes of complete understanding of the present invention, various specific details are set forth, such as specific forms, compositions, and processes, and the like. However, certain embodiments may be practiced without one or more of these specific details, or with other known methods and forms. In other instances, well-known processes and techniques of manufacture are not described in any detail, in order not to unnecessarily obscure the present invention. Reference throughout this specification to "one embodiment" or "embodiment" means that a particular feature, form, composition, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention. Accordingly, the appearances of the phrase " in one embodiment "or" the embodiment "in various places throughout this specification are not necessarily indicative of the same embodiment of the present invention. In addition, a particular feature, form, composition, or characteristic may be combined in any suitable manner in one or more embodiments.

본 발명은 국내 병원 임상 검체에서 아시네토박터 균속에 의한 카바페넴 내성 감염증을 치료하는 목적으로, 상기 균속을 용균시키는 파아지의 전 유전체 분석을 통하여 다양한 용균 효소 유전자를 확보하여 이를 분리 정제하였다. 이를 통해, 카바페넴 내성 아시네토박터 균속 감염에 대한 용균성을 갖는 용균 효소(서열번호 1)를 함유하는 용균성 박테리오파아지(서열번호 2)를 분리하였고, 이를 포함하는 질환 치료용 약학 조성물 및 질환 개선용 식품 조성물을 제공한다. 또한, 본 발명에서는 상기 용균 효소의 아미노산 서열(서열번호 1)을 제공한다.For the purpose of treating carbapenem-resistant infections caused by Ashinobacterium sp. In clinical samples of domestic hospitals, various lytic enzyme genes were isolated and purified by analysis of the whole genome of the phage that lysed the bacteria. Thus, a fungicidal bacteriophage (SEQ ID NO: 2) containing a lytic enzyme having a fungicidal activity against carbapenem-resistant Acinetobacter sp. Infections (SEQ ID NO: 1) was isolated, and a pharmaceutical composition for treating diseases and diseases There is provided a food composition for improvement. In addition, the present invention provides the amino acid sequence (SEQ ID NO: 1) of the lytic enzyme.

본 발명은 대장균 숙주 세포에서 서열번호 1의 용균 효소를 발현시켜서, 정제하는 방법 및 용균능을 측정하는 방법을 제공한다. 대장균 숙주 세포에서 서열번호 1의 용균 효소를 발현시키는 방법은 다음 단계를 포함한다: (a) 검출가능한 레벨의 서열번호 1의 용균 효소를 생성시키기에 충분한 양으로 용균 효소를 암호화하는 유전자를 본 발명에서 목적하는 발현 플라스미드에 클로닝하여 만든 재조합 벡터를 전기장 충격법을 사용하여 대장균 숙주 세포내로 삽입함으로써 원하는 단백질을 대량으로 생산해낼 수 있는 형질전환체를 제조하는 단계, 및 (b) 생성된 용균 효소 단백질을 정제하는 단계: 유전공학분야에서 사용되는 통상의 방법에 따라 상기 대장균 형질전환체를 적당한 항생제를 포함한 LB 고체를 이용하여 37˚C에서 18시간 동안 배양하며, 이 때 형성된 단일 콜로니를 적당한 항생제가 첨가된 LB 배지에 접종하며, 섭씨 37˚C 에서 16시간 배양한 후 적당량을 취하여 LB 배지에 접종하며, 대장균 배양액의 양을 조절하여 OD600이 0.12 이하가 되도록 하고 같은 온도에서 계속 배양하여 OD600이 0.6~0.8에 도달하였을 때 배양액을 18˚C로 냉각시키며, 이어서 발현유도 물질은 IPTG (isopropyl-β-D-thiogalactopyranosid)를 첨가하여 IPTG의 최종농도가 O.5MM이 되도록 하고, 18˚C에서 18시간 더 배양하여 목적하는 단백질의 발현을 대량으로 과발현시키고 발현된 단백질을 정제한다. 암모늄 설페이트 침전법, 페닐 세파로즈 수지 칼럼을 이용하는 정제방법에 의해 단백질을 수득하며, 이에 대한 폴리아크릴아마이드겔 전기영동 및 웨스턴블롯팅을 수행하여 정제된 단백질이 목적하는 단백질임을 확인한다. The present invention provides a method for expressing a lytic enzyme of SEQ ID NO: 1 in E. coli host cells, purifying the lectin, and measuring the lytic activity. A method for expressing a lytic enzyme of SEQ ID NO: 1 in an E. coli host cell comprises the steps of: (a) isolating a gene encoding a lytic enzyme in an amount sufficient to produce a detectable level of the lytic enzyme of SEQ ID NO: 1, Preparing a transformant capable of producing a desired protein in a large amount by inserting a recombinant vector prepared by cloning into a desired expression plasmid into an E. coli host cell by using an electric field impact method, and (b) : The E. coli transformant was cultured for 18 hours at 37 ° C using LB solid containing appropriate antibiotics according to a conventional method used in the field of genetic engineering, and a single colony formed was cultured in a suitable antibiotic After incubation for 16 hours at 37 ° C, the appropriate amount of LB was added to the LB medium Inoculation and sikimyeo controlling the amount of the E. coli culture by OD 600 and OD 600 is continued incubation in a culture solution is cooled 18˚C when reaches 0.6 ~ 0.8, and at a temperature such that the less than 0.12, then the expression inducer is IPTG ( isopropyl- [beta] -D-thiogalactopyranosid) is added so that the final concentration of IPTG is 0.5 mM, and further cultured at 18 [deg.] C for 18 hours to overexpress expression of the target protein in a large amount and purify the expressed protein. Ammonium sulfate precipitation method and a purification method using a phenyl sepharose resin column. Polyacrylamide gel electrophoresis and Western blotting are performed on the protein to confirm that the purified protein is a desired protein.

상기와 같은 방법으로 제조한 용균 효소 단백질을 단독으로 항생제 내성 균주에 처리하면 박테리오파아지를 처리한 것과 같은 용균 효과를 얻을 수 있고, 그 방법은 다음과 같다. 정제된 용균 단백질은 브래드포드 어세이를 통해 정량을 실시한다. A600에서 1이 되는 흡광도가 될 때까지 배양한 항생제 내성 균주를 원심분리하여 인산염 완충액 (10mM K2HPO4, 10mM KH2PO4, pH=7.2)에 재부유시키고 나서 약 105 세포를 용균 단백질 50μg과 혼합하여 최종 부피 100㎕를 만들었다. 이 혼합물을 37˚C에서 1시간 동안 배양한 후 LB 아가 플레이트에 도말하여 37˚C에서 하룻밤 동안 배양하여 플레이트에 생긴 콜로니 숫자를 세어서 용균 단백질의 용균능을 측정하였다. 대조군으로는 용균 단백질이 없는 인산염 완충액을 단독으로 사용하였다. 항균력은 다음의 등식을 이용해 계산하였다. When the lytic enzyme protein prepared by the above method is treated with an antibiotic resistant strain alone, a lytic effect similar to that of treating a bacteriophage can be obtained. The purified lytic protein is quantitated via a Bradford assay. Centrifugally separating the antibiotic resistant strains cultured until the absorbance that is 1 in A600 phosphate buffer (10mM K 2 HPO 4, 10mM KH 2 PO 4, pH = 7.2) and then was re-the floating lysis of about 10 5 cell protein To make a final volume of 100 μl. The mixture was incubated at 37 ° C for 1 hour, plated on LB agar plates, and incubated overnight at 37 ° C. The number of colonies on the plate was counted to measure the lytic activity of the lytic protein. As a control group, phosphate buffer without lytic protein was used alone. The antimicrobial activity was calculated using the following equation.

항균력(%)= (N 0 -N 1 )/N 0 ×100%(%) = ( N 0 - N 1 ) / N 0 100%

여기서, N 0 은 대조군 플레이트에 형성된 콜로니 숫자이고 N 1 은 실험군 플레이트에 형성된 콜로니 숫자이며, 용균능 측정은 3회 반복하였다 (Appl Microbiol Biotechnol (2011) 90:529-539, Antibacterial activity of Acinetobacter baumannii phageΦAB2 endolysin(LysAB2) against both Gram-positive and Gram-negative bacteria).Here, N 0 Is the number of colonies formed on the control plate N 1 was the number of colonies formed on the experimental plate and the assay of the potency was repeated 3 times (Appl Microbiol Biotechnol (2011) 90: 529-539, Antibacterial activity of Acinetobacter baumannii phage AB AB2 endolysin (LysAB2) against both Gram- negative bacteria).

또한, 본 발명에서는 카바페넴 내성 아시네토박터 균속 감염에 대한 용균성을 갖는 서열번호 1의 용균 효소를 함유하는 용균성 박테리오파아지의 서열(서열번호2)을 제공한다. In addition, the present invention provides a sequence of a fungicidal bacteriophage (SEQ ID NO: 2) containing the lytic enzyme of SEQ ID NO: 1 having a tolerance to carbapenem-resistant Acinetobacter sp. Infection.

본 발명의 일 구체예에서, 항생제 내성 아시네토박터 균속에 대한 박테리오 파아지는 서열번호 1의 용균 효소를 제공하고, 상기 구체예의 용균성 박테리오파아지의 기탁번호는 KFCC11525P이며, 상기 구체예의 박테리오파아지는 서열번호 2의 박테리오파아지이며, 상기 구체예의 항생제 내성 아시네토박터 균속에 속하는 균종은 Acinetobacter baumannii , Acinetobacter calocoaceticus , Acinetobacter haemolyticus , Acinetobacter junii , Acinetobacter johnsonii , Acinetobacter lwoffii , Acinetobacter radioresistens 중에서 선택하는 어느 하나이며, 상기 구체예의 항생제는 카바페넴이며, 상기 구체예의 항생제 내성 아시네토박터 균속이 생산하는 효소는 카바페넴아제이며, 상기 구체예의 항생제 내성 아시네토박터 균속이 생산하는 카바페넴아제는 OXA형이다. In one embodiment of the present invention, the bacteriophage to the antibiotic-resistant Acinetobacter sp. Provides the lytic enzyme of SEQ ID NO: 1, the accession number of the fungal bacteriophage of this embodiment is KFCC11525P, the bacteriophage of the above- the bacteriophage of the numbers 2, strains belonging to the embodiments of antibiotics-resistant Acinetobacter is Acinetobacter Species baumannii , Acinetobacter calocoaceticus , Acinetobacter haemolyticus , Acinetobacter junii , Acinetobacter johnsonii , Acinetobacter lwoffii , Acinetobacter radioresistens , and the antibiotic of the specific example is carbapenem. The enzyme produced by the antibiotic-resistant acidophilus germ line of the specific example is carbapenemase, and carbapenem produced by the antibiotic-resistant acidophilus bacteria of the above- Ager is OXA type.

본 발명의 일 구체예에서, 서열번호 1의 용균 효소를 함유하는 용균성 박테리오파아지를 유효성분으로 포함하는 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물을 제공하며, 상기 구체예에서 서열번호 1의 용균 효소를 함유하는 용균성 박테리오파아지를 유효성분으로 포함하는 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 개선용 식품 조성물을 제공하며, 상기 구체예의 질환은 C형 간염, 수족구병, 임질, 클라미디아, 연성하감, 성기단순포진, 첨규콘딜롬, 반코마이신내성황색포도알균감염증, 반코마이신내성장알균감염증, 메티실린내성황색포알균감염증, 다제내성녹농균감염증, 다제내성아시네토박터바우마니균감염증, 카바페넴내성장내속균종감염증, 장관감염증, 급성호홉기감염증, 엔테로바이러스감염증 중에서 선택하는 어느 하나의 질환이다. In one embodiment of the present invention, there is provided a pharmaceutical composition for the treatment of a disease caused by an antibiotic-resistant Acinetobacter sp. Containing as an active ingredient a fungicidal bacteriophage containing the lytic enzyme of SEQ ID NO: 1, The present invention provides a food composition for improving disease caused by an antibiotic-resistant acidophilus sp. G. Comprising a phytotoxic bacteriophage containing the lytic enzyme of SEQ ID NO: 1 as an active ingredient, The present invention relates to a method for the treatment and prophylaxis of a disease, gonorrhea, chlamydia, ductal hypoplasia, genital herpes simplex virus, acycloccinate dilatum, vancomycin resistant yellow staphylococcal infection, vancomycin-resistant bacillus infection, methicillin resistant yellow poplar infectious disease, Bacterial infections, carbapenem-resistant intestinal mycobacterial infections, intestinal infections, acute respiratory infections, enterovirus infections Which it is one of the diseases selected from the.

본 발명의 일 구체예에서, 서열번호 1의 폴리펩타이드를 제공하며, 상기 구체예에서 서열번호 1로 기재되는 폴리펩타이드를 암호화하는 핵산분자를 제공하며, 상기 구체예에서 상기 핵산분자를 포함하는 재조합 벡터를 제공하며, 상기 구체예에서 상기 재조합 벡터를 형질전환시킨 미생물을 제공한다.In one embodiment of the invention, there is provided a polypeptide of SEQ ID NO: 1, wherein said nucleic acid molecule encoding the polypeptide of SEQ ID NO: 1 in said embodiment is provided, wherein said recombinant And in this embodiment, the recombinant vector is transformed.

본 발명의 일 구체예에서, 서열번호 1의 폴리펩타이드를 유효성분으로 포함하는 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물을 제공하며, 상기 구체예에서 서열번호 1의 폴리펩타이드를 유효성분으로 포함하는 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 개선용 식품 조성물을 제공한다. In one embodiment of the present invention, there is provided a pharmaceutical composition for the treatment of a disease caused by an antibiotic-resistant Acinetobacter sp. Containing the polypeptide of SEQ ID NO: 1 as an active ingredient, wherein the polypeptide of SEQ ID NO: 1 The present invention provides a food composition for improving diseases caused by antibiotic-resistant Acinetobacter sp. Containing as an active ingredient.

강력한 항균제인 카바페넴 내성 아시네토박터 균속에 대하여 특이적 사멸능을 갖는 신규한 박테리오파아지 및 이로부터 분리한 용균 효소를 이용하여 카바페넴 내성 아시네토박터 균속에 의해 유발되는 질환의 예방 및 치료 목적으로 활용할 수 있다. A novel bacteriophage having a specific killing activity against carbapenem-resistant Acinetobacter sp., A potent antimicrobial agent, and a lytic enzyme isolated therefrom for the purpose of prevention and treatment of diseases caused by carbapenem-resistant Acinetobacter sp. Can be utilized.

도 1은 다제내성 아시네토박터 균속의 유전체 DNA를 제한효소 Sma I으로 절단하여 전기영동을 실시한 결과이다.
도 2는 도 1의 결과를 OXA-형 카바페넴아제 유전자, 삽입서열 공통 구역1 조성물, 인테그론에 근거하여 작성한 계통수이다.
도 3은 용균성 박테리오파아지 YMC/B1251 ABA BP의 전 유전체를 분석한 결과이다.
도 4는 상기 파아지의 용균성 단백질과 다른 파아지의 용균성 단백질에 대한 계통수이다.
도 5는 상기 파아지의 용균성 단백질과 ABA phiAB2 용균 단백질에 대한 서열을 정렬하여 비교분석한 결과이다.FIG. 1 shows the result of digesting the genomic DNA of the multidrug resistant Ashtonobacter sp. With restriction enzyme Sma I and performing electrophoresis.
Fig. 2 shows the results of Fig. 1 based on the OXA-type carbapenemase gene, the insert sequence common region 1 composition, and integran.
Figure 3 shows the results of analysis of the entire genome of the fungal bacteriophage YMC / B1251 ABA BP.
Fig. 4 is a phylogenetic tree for the soluble protein of the phage and the soluble protein of the other phage.
FIG. 5 shows the result of comparing and analyzing the sequence of the soluble protein of the phage and the ABA phiAB2 lytic protein.

이하, 본 발명의 구성요소와 기술적 특징을 다음의 실시예들을 통하여 보다 상세하게 설명하고자 한다. 그러나, 하기 실시예들은 본 발명의 내용을 예시하는 것일 뿐 발명의 범위가 실시예에 의해 한정되는 것은 아니다. Hereinafter, the components and technical features of the present invention will be described in more detail with reference to the following examples. However, the following examples illustrate the contents of the present invention, but the scope of the invention is not limited by the examples.

실시예1Example 1 . . 카바페넴Carbapenem 내성 임상검체 균주 분리 수집 및 균주 은행 구축 Separation of isolates of resistant clinical isolates and establishment of strain bank

(1) 임상 검체 분리 균주 수집: 인덱스 균주 뱅크 구축(1) Collection of isolates of clinical specimens: Establishment of index strain banks

세브란스 병원의 환자들로부터 호흡기 감염증, 패혈증 및 농양 검체를 수집하였으며 각 검체에 대한 임상적 위중도 평가 기준은 다음과 같다. 호흡기 검체는 그룹 4,5,6으로 제한하였고, 패혈증 검체는 3 쌍 배양 중 2 쌍 이상에서 증식하였으며, 농양 검체는 심부농양 주사기 아스피레이트에 제한하였다. 상기 검체로부터 아시네토박터 균속에 속하는 병원균을 배양 분리하였고, 균주의 동정을 위해 전통적 방법을 통한 생화학적 동정을 실시하였다. 감수성 결과는 Clinical and Laboratory Standards Institute (CLSI, 2010)을 기준으로 판독하였다. 감수성 시험은 Mueller-Hinton 아가를 사용하여 외기 37˚C에서 하룻밤 동안 배양하는 CLSI disk diffusion 시험방법을 사용하였다. 아시네토박터에 대한 시험 항균제는 Imipenem, Meropenem, Ampicillin, Piperacillin, Amoxicillin/Clavulanic acid,　Ampicillin/Sulbactam, Cefoperazone/Sulbactam, Aztreonam, Ceftazidime,　Respiratory infections, sepsis, and abscesses were collected from patients at Severance Hospital. Clinical severity ratings for each sample were as follows. Respiratory specimens were restricted to groups 4,5,6, and sepsis samples proliferated in more than two pairs of triplicate cultures. Abscess specimens were restricted to deep abscess syringe aspirate. From the sample, pathogenic bacteria belonging to the genus Ashinobacterium were cultured, and biochemical identification was carried out by a conventional method to identify the strain. Sensitivity results were read based on the Clinical and Laboratory Standards Institute (CLSI, 2010). Sensitivity tests were performed using the CLSI disk diffusion test method using Mueller-Hinton agar and incubating overnight at 37 ° C in the open air. Ampicillin / Clavulanic acid, Ampicillin / Sulbactam, Cefoperazone / Sulbactam, Aztreonam, Ceftazidime, Ampicillin, Piperacillin,

Cefepime, Cefotaxime, Cefoxitin, Cephalothin, Gentamicin, Tobramycin,　Cefepime, Cefotaxime, Cefoxitin, Cephalothin, Gentamicin, Tobramycin,

Amikacin, Netilmicin, Cotrimoxa, Levofloxacin, Tetracycline를 사용하였다. 카바페넴 내성 균주을 선별하기 위해 Imipenem Hodge test를 통해 카바페넴아제를 발현하는 균주를 1차 선별하였고, 이후에 Imipenem EDTA double disk synergy test를 통해 metallo-β-lactamase를 발현하는 균주를 선별하였는데, 양성 및 음성 대조를 포함한 PCR을 실시하였고 사용한 프라이머 세트는 표 1에 나타내었다.Amikacin, Netilmicin, Cotrimoxa, Levofloxacin and Tetracycline were used. In order to screen for carbapenem-resistant strains, a strain expressing carbapenemase was firstly selected by the Imipenem Hodge test, and then a strain expressing metallo-β-lactamase was selected by Imipenem EDTA double disk synergy test. PCR was performed with negative control and the primer set used was shown in Table 1.

타겟target 프라이머primer 프라이머 서열(5'-3')The primer sequence (5'-3 ') 결과물크기Product Size blabla VIMVIM VIM2FR-F
VIM2FR-RVIM2FR-F
VIM2FR-R ATGTTCAAACTTTTGAGTAAG
CTACTCAACGACTGAGCGATGTTCAAACTTTTGAGTAAG
CTACTCAACGACTGAGCG 801bp801bp blabla IMPIMP IMP1-F
IMP1-RIMP1-F
IMP1-R CATGGTTTGGTGGTTCTTGT
ATAATTTGGCGGACTTTGGCCATGGTTTGGTGGTTCTTGT
ATAATTTGGCGGACTTTGGC 450bp450bp blabla SIMSIM -1-One SIM-1 MP F
SIM-1 MR RSIM-1 MP F
SIM-1 MR R TACAAGGGATTCGGCATCG
TAATGGCCTGTTCCCATGTGTACAAGGGATTCGGCATCG
TAATGGCCTGTTCCCATGTG 571bp571bp blabla SPMSPM -1-One SPM-1-A
SPM-1-BSPM-1-A
SPM-1-B CTGCTTGGATTCATGGGCGC
CCTTTTCCGCGACCTTGATCCTGCTTGGATTCATGGGCGC
CCTTTTCCGCGACCTTGATC 784bp784bp blabla GIMGIM -1-One GIM1-F
GIM1-RGIM1-F
GIM1-R ATTACTTGTAGCGTTGCCAGCT
TAATCAGCCGACGCTTCAGATTACTTGTAGCGTTGCCAGCT
TAATCAGCCGACGCTTCAG 726bp726bp blabla AIMAIM -1-One Yong MBLF
Yong MBLRFYong MBLF
Yong MBLRF GGCATTGATGCGCATCAAGG
GAAGACGTCGTCCGAGATCGGGCATTGATGCGCATCAAGG
GAAGACGTCGTCCGAGATCG 726bp726bp blabla NDMNDM -1-One KP05506 M13 R3
KP05506 M13 R2KP05506 M13 R3
KP05506 M13 R2 CAATATTATGCACCCGGTCG
ATCATGCTGGCCTTGGGGAACAATATTATGCACCCGGTCG
ATCATGCTGGCCTTGGGGAA 726bp726bp blabla HKMHKM -1-One KHM-1 F
KHM-1 RKHM-1 F
KHM-1 R GGTATGCGCTGACGATTCAT
TACCGCATGGCTAAGATTGCGGTATGCGCTGACGATTCAT
TACCGCATGGCTAAGATTGC 526bp526bp blabla SMESME SME1-3 F
SME1-3 RSME1-3 F
SME1-3 R AGCGGTTCCCTTTATGCAGT
CGTGATGCTTCCGCAATAGTAGCGGTTCCCTTTATGCAGT
CGTGATGCTTCCGCAATAGT 661bp661bp bla IMI, bla NMC bla IMI , bla NMC IMI NMC F
IMI NMC RIMI NMC F
IMI NMC R CGATTGGGTAGTTGGCGATA
CGATTCTTGAAGCTTCTGCGCGATTGGGTAGTTGGCGATA
CGATTCTTGAAGCTTCTGCG 173bp173bp blabla GESGES GES 2456 F
GES 2456 RGES 2456 F
GES 2456 R CGAAAAAGCAGCTCAGATCG
TGTCCGTGCTCAGGATGAGTCGAAAAAGCAGCTCAGATCG
TGTCCGTGCTCAGGATGAGT 761bp761 bp blabla KPCKPC KPC 1-4 F
KPC 1-4 RKPC 1-4 F
KPC 1-4 R TGGACACACCCATCCGTTAC
GACGGCCAACACAATAGGTGTGGACACACCCATCCGTTAC
GACGGCCAACACAATAGGTG 515bp515bp

(2) Pulse-field gel electrophoresis를 이용한 색인 계통의 클론성 판정(2) Clonal determination of the index system using pulse-field gel electrophoresis

(Birren and Lai Academic Press. Inc., San Diego, 1993)(Birren and Lai Academic Press, Inc., San Diego, 1993)

시험세균을 Mueller-Hinton 한천 배지에 접종한 후 35˚C에서 12시간 배양하고 살린-에틸렌디아민 사아세트산 용액에 부유하고, 원심 분리하여 침전물을 37˚C에 보관된 Pett IV 용액 500 μL에 다시 부유하였다. 부유액 130 μL와 50˚C에 보온한 2% low-melting 아가로즈 동량을 혼합한 아가로즈 플러그를 만들어 용해 용액 1mL에 넣고 37˚C 온수조에서 1시간 동안 반응시킨 후, ESP 용액에서 15~48시간 반응시킨다. 이후, 아가로즈 Plug를 PMSF(단백질 분해효소 저해제) 용액 1.5mL에 넣어 중화시키고 TE 완충액 1.5mL를 이용하여 세척하였다. 세척한 아가로즈 플러그를 제한효소 완충액 1.5mL에 실온에서 1시간 동안 넣어둔 후에 다시 제한효소 Spe I를 넣은 제한효소 완충액 100μL에 옮겨 넣고 37˚C에서 18시간 동안 반응시킨다. 제한효소를 처리한 아가로즈 Plug를 1% 아가로즈 젤과 CHEF-DRII(Bio-Rad Laboratories)을 이용하여 전기영동을 실시하였다.Test bacteria were inoculated on Mueller-Hinton agar medium, cultured at 35 ° C for 12 hours, suspended in saline-ethylenediaminetetraacetic acid solution, centrifuged and suspended in 500 μL of Pett IV solution stored at 37 ° C Respectively. Agarose plugs were prepared by mixing 130 μL of suspension and 2% low-melting agarose at 50 ° C in 1 mL of dissolution solution. After reacting for 1 hour at 37˚C in hot water bath, 15-48 Time reaction. Then, Agarose Plug was neutralized by adding 1.5 mL of PMSF (protease inhibitor) solution and washed with 1.5 mL of TE Buffer. The washed agarose plugs are placed in 1.5 mL of restriction enzyme buffer for 1 hour at room temperature, then transferred to 100 μL of restriction enzyme buffer containing restriction enzyme Spe I, and reacted at 37˚C for 18 hours. The agarose plug treated with the restriction enzyme was subjected to electrophoresis using 1% agarose gel and CHEF-DRII (Bio-Rad Laboratories).

(2) 균주 수집 및 스크리닝 결과(2) Strain collection and screening results

임상검체에서 분리된 아시네토박터 균속 2831주 중에서 카바페넴 제제인 Imipenem에 내성을 보이는 2173주를 수집하였다. 이들 중에서 변형한 Hodge test를 시행한 결과, 2083주가 카바페넴아제를 생성함을 규명하였다. 이는 카바페넴 내성 균주 중 95.8%에 해당한다. 이들 중 Imipenem-EDTA double-disk synergy 시험을 시행한 결과, 30주가 metallo-beta-lactamase를 생성하는 것을 확인하였다. PFGE를 시행한 결과 3 band 이상의 차이를 보여 클론성이 상이한 13개 그룹으로 구분하였다 (도1, 도2). 13개의 pulsotype 중 4개의 우성은 OXA-51형과 OXA-23형의 카바페넴아제를 주로 생성하였고 OXA-24형과 OXA-58형은 검출되지 않았다 (도 2). ISAba1이 OXA형 카바페넴아제 유전자 위에 모두 검출되었고, 13개의 pulsotype 중에서 9개 군과 11개 군에서 인테그론과 삽입서열 공통구역 1 유전자를 검출하였다.Of the 2831 strains isolated from clinical specimens, 2173 strains resistant to the carbapenem Imipenem were collected. Among these, modified Hodge test was performed to confirm that 2083 strains produced carbapenemase. This corresponds to 95.8% of the carbapenem-resistant strains. Among them, Imipenem-EDTA double-disk synergy test showed that 30 weeks of production of metallo-beta-lactamase. As a result of PFGE analysis, 13 groups with different clonality were identified, with a difference of 3 bands or more (Figs. 1 and 2). Of the 13 pulsotypes, four dominant dominantly produced OXA-51 and OXA-23 type carbapenemases, while OXA-24 and OXA-58 were not detected (FIG. 2). ISAba1 was detected on the OXA type carbapenemase gene, and intetrone and insertional common region 1 gene were detected in 9 and 11 out of 13 pulsetypes.

실시예Example 2.  2. 파아지Phage 은행 구축을 위한 검체 수집 및  Collecting samples for bank construction 파아지Phage 분리 정제 Separation purification

(1) 파아지 은행 구축을 위한 검체 수집(1) Collection of specimens for the construction of phage banks

세브란스 병원의 오수 처리시설에서 최초 침전지를 거친 후 부유물질 및 침사물이 제거된 처리수 2L를 채취하였다. 이는 화학처리 시설 전 단계의 오수로 제한하였다. 수집한 시료에 1L당 염화나트륨 58g을 첨사한 후 10000g에서 10분간 원심 분리하여 200nm 밀리포어 필터로 여과하였다. 얻어진 여과액에 폴리에틸렌글리콜(PEG, 분자량 8000)을 10% V/V으로 첨가하고 4˚C에서 12시간 동안 냉장 보관하였다. 12시간 냉장 보관된 여과액을 12000g에서 20분간 원심 분리하여 침전물을 파아지 희석 완충액 (SM 완충액)에 재 부유하여 냉동 보관하였다. 이를 3회 반복하여 300mL의 박테리오파아지 부유액을 채취하였다. In the sewage treatment facility of Severance Hospital, 2L of treated water from which the suspended matter and sediment were removed after the first sedimentation basin was collected. This was limited to sewage at the pre-stage of the chemical treatment facility. 58 g of sodium chloride was added per liter of the collected sample, followed by centrifugation at 10000 g for 10 minutes and filtration with a 200 nm Millipore filter. Polyethylene glycol (PEG, molecular weight 8000) was added to the obtained filtrate at 10% V / V and stored at 4 ° C for 12 hours in a refrigerator. The filtrate was centrifuged at 12,000 g for 20 minutes for 12 hours, and the precipitate was resuspended in a phage dilution buffer (SM buffer) and stored frozen. This was repeated three times to collect a suspension of 300 mL of the bacteriophage.

(2) 용균성 파아지 선별 및 정제(2) Screening and purification of the fungal phage

가) 용균반 검사를 이용한 파아지 정제 (Kropinski AM et al. In Bacteriophages. Clokie MRJ and Kropinski AM, eds. Humana Press, 2009)A) Phyto-tablets using a flotation test (Kropinski AM et al. In Bacteriophages. Clokie MRJ and Kropinski AM, eds. Humana Press, 2009)

용균성 파아지의 분리 정제는 Spot Test법 (Mazzocco A et al. In Bacteriophages, Clokie and Kropinski AM, eds. Humana Press. 2009)으로 실행하였다. 확보된 균주를 맥콘키 한천배지에서 접종 후 외기 35˚C에서 하룻밤 동안 배양하였다. 배양 후, 투명한 플라크 형성을 보고 파아지에 감수성인 균주를 선별하였다. 감수성인 균주를 맥콘키 한천배지에 접종하여 35˚C에서 12시간 동안 배양하였다. 살린 1ml 튜브에 McFarland 0.5 탁도로 각 균주의 현탁액 제조하고 H 탑 아가 (3 ml), 감수성 박테리아 100ul 및 파아지 용액 (각각 1ul, 10ul 및 50ul)을 섞어 LB 아가에 도포한 후, 35˚C에서 12시간 동안 배양하였다. 플라크 관찰한 후에 파스퇴르 파이펫으로 플라크를 채취하여 SM 완충용액에 희석하고 다시 감수성인 균주 현탁액을 이용하여 3회 반복 정제하였다. 이렇게 얻어진 순수한 박테리오파아지는 SM 완충용액에 희석하고 다시 감수성인 균주 현탁액을 이용하여 3회 반복 정제하였다. 이렇게 얻어진 순수한 박테리오파아지는 SM 완충용액에 희석하여 보관하였고 사용시에 Spot test를 이용하여 각 파아지 용액의 역가를 측정하였다.Separation and purification of soluble phage were carried out by spot test method (Mazzocco A et al. In Bacteriophages, Clokie and Kropinski AM, eds Humana Press. The obtained strains were inoculated on a McConki agar medium and incubated overnight at 35 ° C. After culture, transparent plaque formation was observed, and strains susceptible to phage were selected. The susceptible strains were inoculated on McConki agar medium and cultured at 35 ° C for 12 hours. A suspension of each strain in a saline 1 ml tube was prepared with McFarland 0.5 turbidity and applied to LB agar with H top agar (3 ml), 100 ul of susceptible bacteria and phage solution (1 ul, 10 ul and 50 ul, respectively) Lt; / RTI > After plaque observation, plaques were taken with Pasteur pipette, diluted in SM buffer, and repeatedly refined three times using a susceptible strain suspension. The pure bacteriophage thus obtained was diluted in SM buffer solution and was subjected to repeated purification three times using a suspending suspension. The pure bacteriophage thus obtained was diluted in SM buffer solution and stored. The potency of each phage solution was measured using a spot test at the time of use.

나) 증식법을 이용한 OXA-형 카바페넴아제 생성 아시네토박터 균속의 용균성 파아지 분리B) Solvent-free phage separation of OXA-type carbapenemase-producing Ashtonobacter sp.

LB broth를 이용하여 37 ˚C 배양기에서 하룻밤 동안 종균한 균액에 오수 PEG 처리법으로 획득한 박테리오파아지 부유액을 1차 처리하였다. 이후에 얻어진 상층액을 다시 PEG 처리하여 2차 박테리오파아지 부유액을 획득하였고, 이어서 spot test를 통해 OXA-형 카바페넴아제 생성 아시네토박터 균속에 대한 용균성 파아지를 선별하였다 (표 2). 얻어진 용균성 박테리오파아지를 Kropinski 등의 double agar overlay plaque assay를 통하여 3회 분리 정제하여 순 배양된 박테리오파아지를 확보하였다. Lactic acid bacteria treated with LB broth were first treated with the suspension of the bacteriophage obtained by the treatment with seawater PEG in a 37 ° C incubator overnight. Subsequently, the supernatant obtained was again subjected to PEG treatment to obtain a suspension of a secondary bacteriophage, followed by spot test to select a fusogenic phage for the OXA-type carbapenemase-producing acenetobacter species (Table 2). The resulting fungal bacteriophage was separated and purified three times through a double agar overlay plaque assay of Kropinski et al. To obtain a pure culture bacteriophage.

Pulsotype 및 OXA-생성 Acinetobacter baumannii strainsPulsotype and OXA-producing Acinetobacter baumannii strains PEG 처리 후 증폭시킨 박테리오
파아지를 이용한 Spot test 결과Bacteriophage amplified after PEG treatment
Spot test results using phage #1 (832, YMC/8/11/B6183)# 1 (832, YMC / 8/11 / B6183) Plaque 관찰, 약한 활성Plaque observation, weak activity #2 (748, YMC/8/10/B7070)# 2 (748, YMC / 8/10 / B7070) Plaque 없음.No Plaque. #3 (210, YMC/8/4/B974)# 3 (210, YMC / 8/4 / B974) Plaque 없음.No Plaque. #4 (427, YMC/9/2/B317) # 4 (427, YMC / 9/2 / B317) PlaquePlaque 관찰. observe. #5 (862, YMC/9/3/B162)# 5 (862, YMC / 9/3 / B162) Plaque 없음.No Plaque. #6 (456, YMC/9/2/B1251) # 6 (456, YMC / 9/2 / B1251) PlaquePlaque 관찰. observe. #7 (1004, YMC/9/3/B1744) # 7 (1004, YMC / 9/3 / B1744) PlaquePlaque 관찰. observe. #8 (4286, YMC/9/8/B3635)# 8 (4286, YMC / 9/8 / B3635) Plaque 없음.No Plaque. #9 (1501, YMC/9/4/B73) # 9 (1501, YMC / 9/4 / B73) PlaquePlaque 관찰. observe. #10 (6001, YMC/9/11/B2460)# 10 (6001, YMC / 9/11 / B2460) Plaque 없음.No Plaque. #11 (3075, YMC/9/6/B5007) # 11 (3075, YMC / 9/6 / B5007) PlaquePlaque 관찰. observe. #12 (546, YMC/8/8/B1075)# 12 (546, YMC / 8/8 / B1075) Plaque 없음.No Plaque. #13 (3094, YMC/8/7/B3094) # 13 (3094, YMC / 8/7 / B3094) PlaquePlaque 관찰. observe.

(3) OXA-형 카바페넴아제-생성 아시네토박터 균속의 용균성 파아지에 대한 용균능 측정(3) Solubility measurement for solvent-resistant phage of OXA-type carbapenemase-producing Asnithobacter sp.

각 pulsotype 13개의 index strain 13가지 균주에 대한 용균성 박테리오파아지의 용균력 범위를 측정한 결과, 서로 상이한 용균범위를 가지고 있었다. pulsotype 6번의 균주 ABA 456과 pulsotype 13번 균주 ABA 3094에서 분리된 Φ 456과 Φ 3094는 강력한 플라크 생성을 보여주었다. 특히, 박테리오파아지 Φ456은 pulsotype 4번, 6번, 7번에 모두 강력한 플라크 생성을 보이고 있으므로 넓은 범위의 용균성 박테리오파아지인 것을 확인하였다 (표 3).As a result of measuring the range of application of fungus bacteriophages to thirteen strains of index strain of each pulsotype, they had different range of bacteria. The isolates Φ 456 and Φ 3094 isolated from the isolates ABA 456 and ABA 3094 of the pulsotype 6 showed strong plaque formation. In particular, bacteriophage Φ456 showed strong plaque formation in pulsotypes 4, 6, and 7, indicating that it was a broad range of bacteriophage bacteriophages (Table 3).


OXA-형 카바페넴아제-생성 아시네토박터 균속
OXA-type carbapenemase-producing Acinetobacter sp. 용균성 박테리오파아지를 이용한 Spot test결과Spot test results using bacteriophage phage (-) 물을
이용한 대
조군(-) the water
Used band
Joe Φ51
(LB)Φ51
(LB) Φ427
(LB)Φ427
(LB) Φ456
(LB)Φ456
(LB) Φ1004
(LB)Φ1004
(LB) Φ3075
(LB)Φ3075
(LB) Φ3094
(LB)Φ3094
(LB) #1(832, YMC/8/11/B6183) # 1 (832, YMC / 8/11 / B6183) -- tracetrace -- -- -- -- -- #4(427, YMC/9/2/B317) # 4 (427, YMC / 9/2 / B317) -- +1+1 +3+3 +1+1 -- -- -- #6(456, # 6 (456, YMCYMC /9/2/B1251)/ 9/2 / B1251) -- -- +3+3 +1+1 -- -- -- #7(1004,YMC/9/3/B1744) # 7 (1004, YMC / 9/3 / B1744) -- -- +3+3 -- -- -- -- #9(1501,YMC/9/4/B73) # 9 (1501, YMC / 9/4 / B73) -- tracetrace -- -- -- -- -- #11(3075,YMC/9/6/B5007) # 11 (3075, YMC / 9/6 / B5007) -- tracetrace tracetrace -- -- -- -- #13(3094,YMC/8/7/B3094) # 13 (3094, YMC / 8/7 / B3094) -- -- -- -- -- +3+3 --

실시예Example 3.  3. OXAOXA -형 -brother 카바페넴아제Carbapenem aze -생성 -produce 아시네토박터에Ashineto Bautter 대한  About 용균성Solvent strength 파아지의Phage 전자 현미경 분석 Electron microscope analysis

분리된 박테리오파아지는 에너지 여과 투과 전자현미경을 이용하여 형태를 분석했다. 형태적으로 짧은 꼬리와 육각형 머리(head)를 가지는 단축 50nm, 장축 100nm 정도의 파아지이며 분류상 Podoviridae에 속하는 것으로 분류했다.
The isolated bacteriophages were analyzed for their morphology using an energy filtration transmission electron microscope. It is a 50nm short axis with a short tail and a hexagonal head (morphologically), and a phage about 100nm long. It is classified as belonging to Podoviridae.

실시예Example 4.  4. YMCYMC /B1251 / B1251 ABAABA BPBP 의 전 유전체 서열 분석Of total genome sequence analysis

전 유전체 서열분석을 통해 YMC/B1251 ABA BP의 전 유전체 (45364bp. 62 ORF, G+C contents 39.05%)를 분석했다 (도 3, 표 4). 용균성에 관련된 후보 단백질 (Endolysin, gp51: [Erwinia phage vB EamP-S6]/ 서열 동일성 51%)은 계통수를 통해 다른 파아지의 용균성 관련 단백질과 매우 상이한 차이가 있는 것으로 나타냈다 (도 4, 도 5). The entire genome of the YMC / B1251 ABA BP (45364 bp. 62 ORF, G + C contents 39.05%) was analyzed by the whole genome sequence analysis (FIG. It was shown that the candidate protein related to the fungi (Endolysin, gp51: [Erwinia phage vB EamP-S6] / sequence identity 51%) is very different from phytogenic bacteria-related proteins through phylogenetic trees (Figs. 4 and 5 ).

본 발명에 따른 물질을 포함하는 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 멸균 주사용액, 사전 충전식 주사 용액제의 형태 또는 동결건조된 형태로 제형화할 수 있다. 상세하게는, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트, 수크로스, 락토오스, 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용될 수 있다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제 및 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔, 마크로골, 트윈 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.The composition containing the substance according to the present invention can be administered orally or rectally in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups or aerosols, external preparations, suppository sterilized injection solutions, Or may be formulated in a freeze-dried form. More specifically, when formulating the composition, it can be prepared using a diluent or an excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin, Can be mixed and prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of liquid formulations for oral use include suspensions, solutions, emulsions and syrups. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include withexol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

본 발명의 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 본 발명의 조성물은 1일 0.2 내지 200㎎/㎏으로 투여하는 것이 좋다. 투여는 하루에 한 번 투여할 수도 있고, 수 회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the composition of the present invention is preferably administered at 0.2 to 200 mg / kg per day. The administration may be carried out once a day or several times. The dose is not intended to limit the scope of the invention in any way.

본 발명의 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 주사에 의해 투여될 수 있다.     The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.

본 발명의 폴리펩타이드를 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합체, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다.    Examples of the food to which the polypeptide of the present invention can be added include various foods, beverages, gums, tea, vitamin complexes, health supplements and the like and may be used in the form of powder, granule, tablet, capsule or beverage .

하기에 본 발명의 조성물을 위한 제제예를 예시한다. 단, 하기 제제예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 제제예에 의해 한정되는 것은 아니다.Examples of formulations for the composition of the present invention are illustrated below. However, the following formulation examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following formulation examples.

제제예Formulation example 1:  One: 산제의Sanje 제조 Produce

데옥시시코닌 300 mgDeoxychonine 300 mg

유당 100 mgLactose 100 mg

탈크 10 mgTalc 10 mg

상기의 성분들 및 본원 발명의 조성물을 혼합하고 기밀포에 충진하여 산제를 제조한다.
The above components and the composition of the present invention are mixed and filled in an airtight container to prepare powders.

제제예Formulation example 2: 정제의 제조 2: Preparation of tablets

데옥시시코닌 50 mg50 mg of deoxychoninin

옥수수전분 100 mgCorn starch 100 mg

유당 100 mgLactose 100 mg

스테아린산 마그네슘 2 mgMagnesium stearate 2 mg

상기의 성분들 및 본원 발명의 조성물을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.
After mixing the above components and the composition of the present invention, tablets are prepared by tableting according to a conventional method for producing tablets.

제제예Formulation example 3: 캡슐제의 제조 3: Preparation of capsules

데옥시시코닌 50 mg50 mg of deoxychoninin

옥수수전분 100 mgCorn starch 100 mg

유당 100 mgLactose 100 mg

스테아린산 마그네슘 2 mgMagnesium stearate 2 mg

통상의 캡슐제 제조방법에 따라 상기의 성분 및 본원 발명의 조성물을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.
The above components and the composition of the present invention are mixed according to a conventional capsule preparation method and filled in a gelatin capsule to prepare a capsule preparation.

제제예Formulation example 4: 주사제의 제조 4: Preparation of injection

데옥시시코닌 50 mg50 mg of deoxychoninin

주사용 멸균 증류수 적량Sterile sterilized water for injection

pH 조절제 적량pH adjuster

통상의 주사제의 제조방법에 따라 1 앰플당 (2㎖) 상기의 성분 함량 및 본원 발명의 조성물을 혼합하여 제조한다.
(2 ml) per ampoule according to a conventional method for preparing an injectable preparation, and the composition of the present invention.

제제예Formulation example 5:  5: 액제의Liquid 제조 Produce

데옥시시코닌 100 mg100 mg of deoxychoninin

이성화당 10 g10 g per isomer

만니톨 5 g5 g mannitol

정제수 적량Purified water quantity

통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분 및 본원 발명의 조성물을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ㎖로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.
Each component was added to purified water in accordance with the usual preparation method of the liquid preparation and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components and the composition of the present invention were mixed, and purified water was added thereto. It is filled in a brown bottle and sterilized to prepare a liquid preparation.

제제예Formulation example 6: 건강 식품의 제조 6: Manufacture of health food

데옥시시코닌 1000 ㎎1000 mg of deoxychoninin

비타민 혼합물 적량Vitamin mixture quantity

비타민 A 아세테이트 70 ㎍70 [mu] g of vitamin A acetate

비타민 E 1.0 ㎎Vitamin E 1.0 mg

비타민 B1 0.13 ㎎0.13 mg vitamin B1

비타민 B2 0.15 ㎎0.15 mg of vitamin B2

비타민 B6 0.5 ㎎0.5 mg vitamin B6

비타민 B12 0.2 ㎍0.2 [mu] g vitamin B12

비타민 C 10 ㎎10 mg vitamin C

비오틴 10 ㎍Biotin 10 μg

니코틴산아미드 1.7 ㎎Nicotinic acid amide 1.7 mg

엽산 50 ㎍50 ㎍ of folic acid

판토텐산 칼슘 0.5 ㎎Calcium pantothenate 0.5 mg

무기질 혼합물 적량Mineral mixture quantity

황산제1철 1.75 ㎎1.75 mg of ferrous sulfate

산화아연 0.82 ㎎0.82 mg of zinc oxide

탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg

제1인산칼륨 15 ㎎15 mg of potassium phosphate monobasic

제2인산칼슘 55 ㎎Secondary calcium phosphate 55 mg

구연산칼륨 90 ㎎Potassium citrate 90 mg

탄산칼슘 100 ㎎100 mg of calcium carbonate

염화마그네슘 24.8 ㎎24.8 mg of magnesium chloride

상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분 및 본원 발명의 조성물을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio of the vitamin and mineral mixture may be arbitrarily changed. According to the conventional method for producing health food, After mixing the compositions, granules can be prepared and used in the manufacture of a health food composition according to conventional methods.

제제예Formulation example 7: 건강 음료의 제조 7: Manufacture of health drinks

데옥시시코닌 1000 ㎎1000 mg of deoxychoninin

구연산 1000 ㎎Citric acid 1000 mg

올리고당 100 g100 g of oligosaccharide

매실농축액 2 gPlum concentrate 2 g

타우린 1 gTaurine 1 g

정제수를 가하여 전체 900 ㎖Purified water was added to a total of 900 ml

통상의 건강음료 제조방법에 따라 상기의 성분 및 본원 발명의 조성물을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2l용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. After mixing the above components and the composition of the present invention according to a conventional health drink manufacturing method, the resulting solution was stirred and heated at 85 DEG C for about 1 hour, and then the resulting solution was filtered and sterilized in a sterilized 2 liter container, And then used in the preparation of the health beverage composition of the present invention.

상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Figure pat00001
Figure pat00001

한국미생물보존센터(국내)Korea Microorganism Conservation Center (Domestic) KFCC11524PKFCC11524P 2012030820120308

<110> Office of Research Affairs in Yonsei University <120> Lytic Bacteriophage specific for Acinetobacter genus resistant to carbarpenem <130> IPDB46201 <160> 2 <170> KopatentIn 2.0 <210> 1 <211> 181 <212> PRT <213> Bacteriophage for Acinetobacter genus <400> 1 Met Asn Ile Glu Lys Tyr Leu Asp Glu Leu Ile Lys Arg Glu Gly Gly 1 5 10 15 Tyr Val Asn Asn Pro Ala Asp Arg Gly Gly Ala Thr Lys Tyr Gly Ile 20 25 30 Thr Glu Ala Val Ala Arg Ala Asn Gly Phe Lys Gly Asn Met Arg Asp 35 40 45 Leu Pro Leu Asp Val Ala Lys Ala Ile Tyr Arg Lys Asn Tyr Trp Thr 50 55 60 Ala Pro Arg Phe Asp Gln Val Asn Ile Ile Ser Ser Ala Val Ala Glu 65 70 75 80 Glu Leu Leu Asp Thr Gly Val Asn Cys Gly Thr Gly Phe Ala Lys Pro 85 90 95 Leu Leu Gln Arg Ala Leu Asn Leu Leu Asn Asn Asn Gly Lys Ala Gly 100 105 110 Trp Pro Asp Leu Ser Val Asp Gly Ile Tyr Gly Pro Ala Thr Leu Asn 115 120 125 Ala Leu Lys Thr Tyr Leu Val Lys Arg Gly Lys Glu Gly Glu Lys Val 130 135 140 Leu Val Arg Val Leu Asn Ile Met Gln Gly Gln Arg Tyr Ile Glu Ile 145 150 155 160 Cys Glu Arg Asn Pro Ser Gln Glu Gln Phe Phe Tyr Gly Trp Ile Ala 165 170 175 Asn Arg Val Ser Met 180 <210> 2 <211> 45364 <212> DNA <213> Bacteriophage for Acinetobacter genus <400> 2 taaaatattt atgtttttat ggtcgtcatg attggtgaaa tcattccaag gtttgccgct 60 taagtcagtt actgactcaa tagcaaggtt agtaatttca gccgctgtaa aatcagatcc 120 agctacacca tagctatcag ctacaccgtc aaaatcgaag ctcacgttta atttgaagcc 180 gtcaatgcgg ataactgctt caccagattt ttctccagtt ttcttaacag ccagaagttc 240 atattcagaa gcaacgactt gctcgctttc atatgagtaa ttagaaggga cgctagaatt 300 agcagttcga tattcacaag aactcaaggc tacaagtaca gcaattgctg taactccagt 360 taccttatgc ttgtttgaaa aggtttttac gttcataatt gatctcgcag tttgcaaaag 420 cacatcggac ctggggaggg cggtgtgctt ttttgttgtc tgtgagataa atataagaaa 480 acttattttt attgtcaata agaaatctta tttaaattta agaaatctta tttttatgct 540 ttaatagaca aaagaaaacc cacacggggt gggttcgaag gggggattag ttgtaatttt 600 gaggaagttc ccataatgct tctgtcttta gacgcaattt tttttgattt tccttgagac 660 tattctcaat ttcctttatt agtttatgtt gttttactat ttgatcttta acctcttcag 720 gaggattcgg gatctcaata ttcaaaaaca tttcatcagg aatactgcgt cgtctctcta 780 cactgccttg cattttactt ttgtatattt ttcttagaga attagatctc aaaatcaaat 840 ccaaatattc tacattaact tctcgtttta atctaaagat tttgtatgct gggcttacgg 900 cagcagcatc gtaatatttt tgaaatccta gaacaccttc atctataggg aaccccatta 960 caagttcatt tttaaaaacc tttttatacc cagaaatatc agaacttgcg actcgttttt 1020 taaatttctc atgctgatca attaagccat gttccatagt gatactcata ataggtatat 1080 ttgtatcctc tcccactttg actttgccag acaaggatag gagttctttt agttttatag 1140 ttgggaattt tgattttata tgtgaattac tatagtgagc ataattataa atataatcat 1200 tgcttctgat taattctgga ttaactttta agaaacctaa ttcattataa tatttatcaa 1260 agtcgctctt atttaaatca gcaaaatcta aattttttaa atcattttcg tcaatttttc 1320 tacggaaaga atctaaactt aggccatcat ttgtcacatt gtagtaaaaa acgtcagaat 1380 ttgttctacc attatgacag ttggtaaagt agagtatatt ggttttaact tttgcatatg 1440 gcagaaaaac ttcttttgga agtgaaacta ctgcttttag ttgggcgttt tcaaataaat 1500 acttccttac tggagctaaa gcggctttaa aaagaaagcc ttcaggtact actaatgcca 1560 ttcgccctcc tttttttgtt gctttaaagc aatgtagaac acatactcca tcaccatcgt 1620 ttttagctaa cttattctca tataagtgag aataagaagt tttttgagaa aatggcatgt 1680 tggttataac cacatcatat tcagattcaa tagggttttg aagtgtgtct atctggcaaa 1740 ttccactatg cccatcccca tgcagaatca tattcatttt tgcgagtttt gcatttgagg 1800 taatttctct tccaaaaata gtattatgtt taagcttgat ttcttcacta ctattgtttg 1860 caattaaagt gttatctttt atatgatcaa atgcctctgt taaaaaacca cctgtcccac 1920 aaaaagggtc atagatcttt tcaccatatt tagggttgac taagttaaca atggttttag 1980 ttatgtgacg tggagtaaaa tattctccta agtcattatt agttgctgta gcttgctgta 2040 agaaatactc aaaagcatct cctttaatat cggtatctat tgatgagagt tttaacttat 2100 ccaactcttt gatcatctct ttaacagcaa cagggttggt tagctgtaaa tttgtaaaaa 2160 cagaagcacc atattgtcta tcaatatctt gtagtatgtt attagttgta ttaattagca 2220 aatcattatc gagacttttg agagaattcc aaatacctgt attagcattc tctgtataca 2280 attttaaaaa aagaatgttt gcaaattctg aaagcctttc tataccagct cttaaacctt 2340 cacctcttag tgagttattt aacttcttga aaacattaat taactctttg cgagagacta 2400 aaatttcttt aggtgtaata taaataccat ttgtttcctg caatatgaac tctttagctt 2460 catttactct tattaattca ttaacctcat tttcatcaat aaataatggt ttttgggtat 2520 acaaatgccg tgtttcgcag aaaccattat tcattgcaaa tatcaaaggt gcatcaagca 2580 tttcagcata ttcggttgcc tgatccagtg cttttgttaa gctttttcca cctgatttcg 2640 tttcaattac accgattggc cgcttatttt gtgaatcgaa aagaacataa tcgggtcttt 2700 ttttactttt cttgagaaac tcattattaa caattcttaa gatatctgat tcaaaaaaga 2760 catttttgtt tggatcttga atgtccaaga tccagccctt gttaatcaaa ttattgttaa 2820 caataaaacg tgtatcttgc tcaatattag acatattgca taatcccaat atctactata 2880 aaaactattg gcaatctaca cattacacac taaaacatca ataaatatta ctatctaata 2940 agtgatatac cccacattta aaagactgtg tcgggttcac agtttattaa tctttggtgt 3000 tattaatttt ctgacctagc tttccttctt ttaccaactg cacgacctgc tcattagtaa 3060 gcacaggaat aaagactttg tcgccaatat ctttagaaag aatctttact tcttcagcgg 3120 ttagcaccaa agcttcacca tgtttagcag catcattgat gcgagcaata atctgattga 3180 ttggtagttt agagttgtcc ataagtcttc ctgtgattaa tgcgaataag gatgttcttg 3240 tctgtgctga cttggcggca cgatatctgt aatagcggta atactttcaa cctcgtccat 3300 ttcaaagaaa aatcgctcac caccattcac agaaagcaaa cttaaaaccc caccattgat 3360 gccgacaaat tctttaattg tgcatcttcc atccttcaag cacacctgaa caaactcatt 3420 cggcacaagc tctgcatctg gatcgcaaac tacataccaa ccattacgaa ttgctggaaa 3480 cattgagtcg ccagtgcctt taataccata ggctcttggt cctgctgagt gagttggaac 3540 ataaccatca ccaccgttac cttcgtaacc catatctgtg aaatacccat ccatacccat 3600 ctttgaatag gctttaacag gaacgtatct tttttgggtg gggaatggtt taacaggtgt 3660 ttcaataaat ttaacagcat cttcgctatc gggaatattg tattttttct taaaagcttc 3720 gatatccaga actttcaatt gtgcaacagt gctatccaac ttgggaccgc tttcatctcc 3780 attagttata tacgaagtcg acactccgaa ataagcggcc attttgctta atgggtctgc 3840 tttaggagca taagcatctt tctcccaacc agtaacatta ggcgcactaa ccccagcgat 3900 ttttgccaac tcgccttggg ttaatttctt ttctcttcgt aaggcgcgaa tacgctgacc 3960 catagtttct agattcttca tataagttat cttacatctt gcaaaaataa gttatctttg 4020 ttttaatact aagaaatctt attttttgag gttgcacaaa tgaccaaaca ggaagcttat 4080 gagttgcttg gtgtcaatgg tgttggcttg gcaaagttat taggaattga accacctgct 4140 gtttaccagt ggtcaaatga aaaaatccct ttagctcgcg aataccaaat cagagacttg 4200 gcaaatggca aagagccaat caaacgaact acttcaaatg cttaggacct aaccatgagc 4260 aaattatcag ttgatatatc tgcaagcgcc agaaatggcg tatcccgcat attgcatggt 4320 cttgatataa gcaaccaaaa agagattgct gaacaattaa aagttgatcc aagcactatt 4380 actcggctta aaacagataa gaaaaacaat ggcttgaatg aaattgaaat gttttgcgag 4440 ctattgagct tgcttggttt aaaagtcgtt cctaaagatt atcagagcat tgataaagaa 4500 cgggttgctg cacttttagt catgtctaaa agctggatga accgtattga aacagtggat 4560 gacttatttc acgacgaaat cagcgttaag aaagaaaagc ttggatatta aaaaccacta 4620 cctgcgcgaa caggagtggt ttcgcattca caaatttagg aacccatgaa tatgcaaaac 4680 aatttagcaa atcaatcggc taattacaac acaccagaat ttatacctgg tgacgttgta 4740 gtgcttacta aagagtgccg tactttcaaa tcaaatgatt tgtttgaagt taaaaataaa 4800 actttgacta ggttgtggac tatcaaatcg gagaatcatt tgattctggt ttcatcaaaa 4860 gaaatccgta cagcaacagt agcagagctc aacgctaaac gccgcctaac aaaagctgag 4920 caagcattag cggaggtgtc atgaacagct ttacacacca aatcaaagat tctcgccagc 4980 aaagtgaaat ccaatctttc tatgagcctg cattgcgagt acttggccac ctatttgagg 5040 tgaaaaagca aaatttacga aacaaggggt atgacgaaaa taatgcggcg gtaaccaagg 5100 ttgaattttc agaggctatg gctcgtcaat ttcgcataac gcagtggtta gcacaacaga 5160 ttgtaaccag cttaaccaaa gcgtgtttgg ttgattcgtt tggtggctat gttaagccaa 5220 aggatggtga aaagtgagat atgcagcaag aagaaaacag gatatttccg tttccaccac 5280 accgctagag gtggtaattc cactggaaca accagtaaag atctattcgg ctaaagaatt 5340 agcagccatg ccgctttcag ttatgaatgc cgcaattgag gctcaggaaa gattttatca 5400 acttgaagaa ttaacccata tgggggggca ggctatagca gttcgccgtc tcatggagga 5460 tgggcacaaa ctaattcagg tgaaagaaaa gtcgcgcatt cgctacaaaa tcaacaacga 5520 atttattcct ccaagaatta ttcgtcagtt ggaaatgcgc ggattagtga agcttgaaag 5580 gggtaagtaa tgattattat caccacttca aagccccttc gaaccccctt caaaggagat 5640 aaataaccat gcgtgactat gggaaagtct caccacattt ctggacggga actacgggaa 5700 aaaaacttcg tcaaacacct gaaggcttaa ttgtcgctat gtatttaatg acaagccctc 5760 acgcgaacat gcttggcttg tattacatac cccttctata tattgctcat gaaactggct 5820 tgggctttga aggggcttct aaggggcttc aaagagcctg tgaagcgggg ttttgtagct 5880 atgacgaagc cacggagaca gtctgggtgc acgagatggc acgttttcaa gtagctgagt 5940 cattaaagcc agccgataac cgctgtaaga acgtgcaaaa agagtatgat tcattgccgt 6000 caagccctta tttatcaagc tttttcgata aatatgcaca agcattttgt atgactcaaa 6060 agcgtggcga aaacgccaaa atagatagcc ccttacaagc cccttcaaag ccccttcgaa 6120 gccaggaaca ggaacaggag caggagcagg agcaggaaca agaaaatact cacacacaaa 6180 acgcggttga aaatttttca gcggccgagg agtcttggaa accaaatcgt gaactattgc 6240 tgaatgttct taggacttca caagtgggtg cacaagcaga gcaggtttta aaaatgccaa 6300 attatgaatt tcatcttggc aacttcaatg ctcactggga aaacaaaatt gatctcacgg 6360 aaaaccaacg aactcgaaag tttgcaactt ggttaattca ggaattcaca aagtcgataa 6420 gacctaaaaa acaaaactca ccaatgaaaa ctgcaccagc aagagacgta aacagtgctt 6480 ggggtgatgc aaaacagtat gcaccagcca cagatgatat cgatgtaggg gagatgctat 6540 gaatgcattg agcaaacaat tcaaaactga gctggtacaa actaatcagt tttgccctaa 6600 acacaatgag ttaatggttt tactaattgg tcgtccagtt tgccaaacat gtgcaaatga 6660 agcgtatgtg aaatcacaaa ttgaacacgc acaccaagtc aacctcatgg tacgcgagaa 6720 acattttgcc ggagcaaaac tccctgagcg ccacaaggaa agcggattta aaaattatat 6780 ggtgagtatc gatccacaga aagaggctaa agctgcttgc cataaatttg ttcaagattt 6840 taattcaggg aagaagcgca atctgattat ggttgggcgc acaggaacag gaaaaaccca 6900 tcttgcatgt gctattgctc gtaacgtttt agacaagcgg agttatgttc gttacgtcac 6960 ctcagaagac atggcaaatg aaattgccac tgcatggaca aagcctgatg acaatgaagc 7020 aaatgcaatt tttcgcttca cggactgtga tttattgata ttggatgaat atggtttgca 7080 cgaccaacac gagagtcgat tgcagctcgt tcataaagtt ttatatgcac gttatgacga 7140 aaaaaagccg acagttttaa tttccaacat gacgcttgag tctacagaaa aggcgcaagg 7200 tttgaaggaa aacttagggg accgtttatg gtctcggttt caacatgacg gtttgacagt 7260 agttgaatgt gactgggatg acttgcgttt tggtggggca ggatcatgac taaattcgag 7320 attttaagct gtggcttact catttcgtgt gtaacagcag tactttgcgg tgcggtggtt 7380 ttgtggtggt tggcgcgtaa agagcttgat gagaaaggag ccagccatga aagcaactaa 7440 attgattaga gataaaggac tgcaatacgc gaaggaaatc gtagattcag cacccgataa 7500 cgcaactgaa tggaacgagg gttatgagtt ccaatgtggt caaagtgtag aaatcagccc 7560 agcagatcgt gagaagtatt ttgtagattt ggttgagctt aaacgtctgg tggagtcttt 7620 gaaaatcatc aacgatttag gtggagttga gaagctaacg cctgcattca ttacgacaga 7680 taagcatgtt ggttacacgc atgttcgcat ggtgggaaat gggagattga gctttcttga 7740 tgatttttgc gacttcattc cagatggttc catttcaatt aagcgtgtga tgactgctat 7800 ccgcgaccac gaatcaatat acggaggcgg tgaatctcat gccaactaga tataacacag 7860 gcgagtatag ctacgatctt gaatatcact atggagatat gtcagcaagc atggagatgc 7920 ttagagcacg tttaattgaa ttgttgactc ctcatctgtc tggccgttat gtgaaatgga 7980 gagaagcata tttcacaagg tttacaaagt gcggcgggga ttcggggtgg atgttttgtg 8040 taggtccaca cgaatttcat attgatgggg cgttaaggcg ctattactca ggttctattg 8100 atattaccta caaccagaaa gatcgatatt tcttggtggg tgagaaaaga aagtcaaatg 8160 taaggcttgt aaggggtttg gcttcattcg agatgatggg tgggggcata tagataaatg 8220 tgaaatgtgt gatgcagaaa aaggagccag ccatgagtga gtttgagggt aaatctggaa 8280 agtgggcttg ggagattcaa aaagaacaac aagcgaaagt ggaggagctg caaaagcgtt 8340 tagatggggc attaaaagag actcaatatg ctttgcagta tgttgaagaa gacatgcgcg 8400 gcaatcatga atttctacaa atggcaatga ttcgaaccct taaagctata gagcaagtgc 8460 tcaaaggtgg tgcttgatgt catcagtcag cattgctgaa taccgcaagt tatttcccat 8520 aaagaaaata aaaagcgccg ttcagcaaag caagttgcca gacaaccaag tgtgggtgaa 8580 gtggttctgg caacgcattt aagagcatgc aagattggat ttgaacagga atataagttc 8640 catcctgaac gcaaatggag agcagatttt ttaataaagg gttcaaagat tttgattgag 8700 gtagaaggcg ggatctggag cggaggccgt cacacaagag gcaagggcta tttaggggat 8760 atggagaaat acaactccgc agcaatgatg ggttttacag ttttacggtt cagtacagag 8820 caagttaagt ccggtatggc attaaagcaa attgaattat taattaaggg taaataggaa 8880 ggcgattatg ttggttgaaa agtttgattt tattgagtta cttcgccttg ctattgctca 8940 aagcgaaggt aaagggaaaa ttactaagca tgttgttttg ggagaaattg ccttattgcc 9000 tgcaggtgca aaaaaatggg cagaattact gcttgaacgt attgattttg agcgcattgc 9060 agaaatcaca gaaacaaaga aaatttatga gaccaggata attaatggta aggaatcaaa 9120 aaagcgtatt ggtgaaatac cgggtaaagt tgaaataaaa aaaggggaga ttaactcagc 9180 tgattttttc cgcgttagaa acgtactagc gggtaagatc catcgtgaaa tgatcaaaaa 9240 gaactttaag ccaaataatt gtcagggcga tttatcaaat gtggccaaag gtattgctga 9300 ggttgttttg cgtgggcgat tatttacaaa ggcaatgtgt ggccattgcc agggattagg 9360 caaattggag ttatttaatg aaaagggata tccaagcgga tctaagtttt gtgataaatg 9420 cagtggtacg gggaaacgcc catatacatt gcatgaaaaa attacgatcg caaaattaaa 9480 agtgtctaag tctggttatt ctgagcgata tgaaccatat gaattaattg ctgaagcatg 9540 tatcgaaaat tgggaaaaca ccattagaac tagcctggct agatcgtttc attttgaacc 9600 tgaagaaata tcattagctt gacttaaaca gaacggttga gtataagtat ttctaaaatg 9660 ggcgctttat acatggatcg cctgaaaaac ttaataaaag ctcactaatt ttagtgggct 9720 ttttgcgtat ctagagcatt gaaaatggaa aacacctggc atgctgacca agaaaaacca 9780 gaattacggc cagatgaaaa acctttgaat tgcccatttt gtggatctga ttcaatttgt 9840 acggattctt cacattatgg aaaaccagat gaagacggct ctatagcgtg ggatgctttc 9900 acatggtgtc atgattgtgg atcaaaaggc cctagtgctt gggcgatgat cgcttgggat 9960 gaaaattttc attacgacac tgtttatgaa gaaagatcaa ttgttaatta tgctattcgc 10020 cagtggaata cacgcaaata agatttttaa tctcgtgagg ggtgttttat aagcacacct 10080 ctcttttagc cggacggatt acggcgcaaa cggccccgct acatactagt tattggcggg 10140 gctttttctt tttggagtat gtatgactga atttcaaaaa attacgcatg agattagaca 10200 gctccaagta gagttaaatc atttaggaag ctgcaataca aaagacttaa cagcagaaca 10260 gatcgctcac atagatgagc gatttttttt ggccattgaa aagcaaagta aattaattgc 10320 tcgtctcaac aataagccag agggcttctt ataaatattg gtggtgcgat ggatcctaaa 10380 aagtactata tgctcaccag gaaaaaagaa agaaaaccca agccaaagag cacaccatta 10440 ccaaaagcca agcaaaacta tttagaggcc gaagcaactc taaaagaaga attaatcgag 10500 ttggccattg gttttgaaag taagtttcag ccgatccata ccaaacactg gcgctttgat 10560 tttcatatag tgaaattgcg tttgctcatt gaaattgagg gtggtccctg gtctggtggg 10620 cgtggtggaa agctgtcaaa taaagcatgg agtcttaatc gatatgatca tgctgaagag 10680 atgggttaca aaatagagcg ctttcatcca gattctattt tgtcgggata tgtcatcaac 10740 tggataaaaa gtgaattagc gagaattgaa gatggagcag atcagaccat ttcctccaac 10800 tgattttatg gatcaggcag aagaagagga agcaattcgt ttaatacccg ctccagacct 10860 aaagaaatgg gttgtggcca actacttaac gataggtgga cctctttata accctgacca 10920 tgaccatatt gctgagctgc ttcacgataa tgaagaattt ttagcatttg cttgggcctc 10980 ttctgcatat aaaagtaagc aagctatggt gttaggtcag tgcgaaaaag tcatgttcaa 11040 tgttggtgga tggcgtaagg ccagacaaga gcaacagatg cgtgattggt ttggttttgt 11100 acctacttat ttaataactg tcgacgcttc tttctgtgag cgtgcaaacg atacagagtt 11160 ctgttactta cttgaacatg agctttacca cattggagtg atgagagacg aggacggaga 11220 aattgtttat agcgatagtt ctggtcttcc taagcactat cttgctggtc atgacgttga 11280 agagtttatt ggcgtagtta aacgttatgg accaagcaaa aatgttaagc gacttattga 11340 agtcgcaaaa aatccgccgt ttgtttcgaa tcttgatatt tcaaaatgct gcggcaactg 11400 tgtaatcaat tgagcctaat ggctcttttt tttgcccatt ttgttatacg tagttatacg 11460 atgaggaagt tatggcgaca ctaaaagagc ctgtgaaaat ctttatagtt cagtctcttg 11520 cttgtcgtga tacacctcaa gaagtggctg aactcgtaaa acaagagttt ggcgttgata 11580 tagatcgtgt tcaagttgca acttatgacc ctacaaaggt tgctggtaag aacttaagca 11640 aaaagtatgt cgaactattt gaaaaaacca gagatgagtt tgataaaggc ttaattgata 11700 ttccaattgc taataagtac taccgattga agcaatacca aagacaactt gagaagacta 11760 gaaacgtcaa aacagcctta aaaattcttg agcaagccgc taaagacatt ggtggtcaat 11820 ttactaatcg ccaagaaatt acaggcaaag acggcggacc agtccaaaca gttaattcag 11880 aaattccagt tccaatggaa gattacttaa aagcgcggag ggaagtctta gatgagtact 11940 gatgcggctc gggataaagc catccggatc gaggcgcaag aagatttata tttcttcaca 12000 aggtacatgt ttaaggagcg ccgtggttat aaatggatgc aaaattggca ccacttagaa 12060 atctgcgaag ctttaatgaa agtttatcgc ggagagataa agcggttaat tattaacgtt 12120 ccaccacgat attctaaaac tgaaattgct gtaattaatt tcatggcttg gtgttttggt 12180 aagaatccag actgtgagtt tattcatatc agttactcgg caatgcttgc cgcaaataat 12240 gccttccaaa tacgaactct tgtacaagaa gaggcgtata gaaaagtctt tcctgagctt 12300 acattgcgtg atgatagtaa ggctaaagac ttctggagaa cttctcaagg cggtgtctgc 12360 tatgcgacag gtacaggcgg tacgattact ggttttggtg caggaaaact tcgtaaaggc 12420 tttggtggct gcattattat tgatgaccca cataaagcac atgaagcttc atcaaaaact 12480 attcgagaag gggtaattga ttggtttcag aacacactcg aatcgcgtac taactcgcca 12540 gatacgccga tcattgtgat tatgcagcga cttcatgaag atgatttagc tggatggttg 12600 ctaggtgata gaaaagacgg cgttcctgta gctggtggta acggtgaagt gtgggagcat 12660 ctatgtcttt cagctattca ggaagacgga tccgcactgt ggccagcaaa acacaatatc 12720 caaaaattga ggctaatgga gcaagcagca ccatatgtat ttgccgggca gtaccgacaa 12780 atgccatcac cgccagcagg cggttttttt aagcccgaca atattcaaat tgttgatgct 12840 ttgcctgcgg atgtagtgaa acaagttagg gcttgggatt ttggggctac cgaaaatgag 12900 ggcgacttta cagtaggtgt gcgagaagct ctaggcgcag atggttttac ttacattgtc 12960 gatgtaacta gaggacagct tggacctgac aatgtgaata agcgcttaga acaaacagca 13020 aaaatagatg ggaaaaaagt ttctgtgcgt ctaccacaag atcccggtca agctggtaaa 13080 tcacaagcta gttcatttgt gaagcttctt gcgggttata gcgtgatagc taagccaatt 13140 tcaggtgaca agcttacacg tgcacaacca tttgcggccc aagttaacgt aggaaatgta 13200 cgaatgctca aaggtgaatg gaataaggat tttattgatg agcttcgtca ttttcctaat 13260 ggcacacatg acgaccaagt ggatgcagct tcagatgcgt ttaatgaatt acatgaaggt 13320 tttgaagcct tctttgctga tatgggattt gctcgatgag tgatgtaact tttcaacatg 13380 ctgaatatgt taagaacttg ccatactggc aaaaacttga tgatgtttgt gaaggtgaag 13440 atgcagttaa ggctaaaggt gaaaaatatt tgccgatgcc aaatgcacat gataaatcac 13500 ctgcaaataa aagcgcttat gaggcttatc ttacccgtgc agtcttttat gaagtaacag 13560 ggactacatt aaatagttta gttggtgcag cttttgcaac cgatccaagt tttaaatttc 13620 ctccggaact tgctcattta gaacgtaatg caaatggtgc tggtttaagt acttatcaat 13680 tggctcaaaa tggaattcgc catttattga agcattatcg ttgtgcttta tatgtagatt 13740 atcctgatgt gccgccagct cgtaatctag cggaatttaa agcacaaaaa gcctatccga 13800 tgattcattt actaaatgcc cttgatgtag tgaattggga ttcagtaatg atcgataacc 13860 agaaaaagct ttgcttagtg gttatacgtg aatttaagtc tgagcgcggt gctgatggat 13920 ttagtaaaac cgaacaagag caatatcgtg tacttcgttt agagcaagag ggaaatgggg 13980 aatatattta ttccgttcag gtgtacacaa agggtgaaaa gggtaactgg gttggcggag 14040 agaagaagtt tccaacagat tacaacggga atttctggac ctatatacct tttacatttg 14100 taggtgcaat tgataattca gaagagatta aaaagccacc attacttcct ttggctaatc 14160 tcaatttagc ccattacaga gacagtgcgg actttcaaga gtccgttttt tatatggggc 14220 aacctcaata ttatgcgaag ggtgttaatt gggagtggta tgaccaagcc aagaaacgtg 14280 gcatctacat tggagcgaaa gtacttttgc ctttacctga aaatggtggt ttaggaattg 14340 tacaagccga ccctaatact cttgcccggg aagcgatgaa agataagtgg gaaaaaatga 14400 aggagatggg ggcgcgttta attgagaagg gctcgggaag taaaaagacc gctaccgaag 14460 cgaatagtga tgacgccgtt cagcattcag ttctttcgct ctgtgtcgtt aatatgaatg 14520 aagccttgtc agcagcatta cgatgggctg ctaagtttgt aacgcctaat gtggatgttc 14580 taactaaaga tgatttgatg ttcgaaatca gtcaagaatt taacaaacag ggttatttag 14640 ctgagttagc tcgacagtta tttgaagcag ctctacaagg ccgatcttca tttaaatcat 14700 ggtgggaata caaccaaaca ggtatgttcc ctaaacaaaa atatgaagaa gagcttcaga 14760 atgttgaagc agagcaagat gggactttaa atcaaaaggt agagtgagat ggcaacagat 14820 atcaaaaaac tatttgaagt actcactcag caccaggcct atctttatcg tgcttcatca 14880 aaaacggtaa atgagttatt ggctttattc aatgatgata cgagcaagat gctatctaag 14940 cttcgggatt tattggatga gcttaatgag tcggagaaag ttgctttagc tggtggtaaa 15000 tatacaactt caaatttaag ggaaattagg gatttgattg cccaatggtt tgccagtgtt 15060 aatttagcat tacctgaagc ttttgccgtt tctgctacgg cgctggctgt ttatgaggcc 15120 aattacgtag ctaagctcta tggagcaaaa attaataagc ctgatgggga aaaactattc 15180 ttatccgcta aaaaagttcc gttggcaggt ggcgctcttg tcgatgatct gctttcaaga 15240 attgctgaaa gtgcccgtca aaaggttgag tatgcaattc gagatggtat taattcaggc 15300 aaaactaacc aagaaattgt tcagcgtatt cgtggtacca aacggcttaa ctatgaagat 15360 gggatcttaa atggtaccaa aactgatatt gagcgaacgg taagaactgt gcgaagtcat 15420 gtagctaatc aagcctatct aaatagcttc aaccaaattg gctttgaata tgtccgattt 15480 gttagcgttt tagatggacg aacttctaag ctttgcgctt cattagatgg ttcagtgtgg 15540 gaaataaatg atccggcaaa gcgagtgccg ccgttacatc ctaactgtcg cagtatcttg 15600 gttccggtcg agaaggacgg tcaacttgtt ggcgaacggc catttgtaat ggacgaacgt 15660 agagttaaag acatccccaa agaagagcga agccagttaa taggacagtt agatgcaaac 15720 accacattca aagagttctt taagaaaaca gatgatttct ttcaaaggga gtggctaggg 15780 ccaaagcgct ttaagctcta taaagatggg aaatttgatt ttgataagtt ctttgatcct 15840 gaaggccgtt tctatagctt agatgatttg agaaagttgg atgaaaaagc ttttaaaaag 15900 ttgggtctgt aatttttctt atgttatatt ttttaaaaca tcagaattta tacaatatga 15960 aaacaatagc ttttgtatgt ctaaccctaa tttccatcac ttgtttagct gaaccaagtc 16020 aaaaatatct taaagaatat gatcgattgt ctgaagcttt ggagtcagca atggcaaatg 16080 catattcttt tgatcctgca actggtcaag taaaacaggc tactcaaggt ttagaagcta 16140 aaaataattt atgtagagct gcccaggcga aactaaacct caccacgttt ttaaaagaca 16200 atttagagga atctaaagag ctttataaat ctattgatgg tgcagagact ctagataaaa 16260 attatcttag tggacaacag caggaacaac aaaatctcgt ttcaaatttg aaaaaagacc 16320 ttgttggaac tggatttaac tgtgagtaat tattgccgat tacaggtaat tctaaactca 16380 cttaagacac aattttcacc tatataagcg cccaaatggc gcttttgtca tttatggagt 16440 ttggcttatg agtgaatcaa aagttagaca tttggtactt aaaagagttt cagataaatc 16500 ttctcatctt gctctttgtg acgaggaaac aggtattcca ttagctggat taaccgctgt 16560 aaaaatgaat tgtagtgttt ttgagggtcc agcgactatc acggcaacat ttgatgtagg 16620 tggtcctcaa ggcatccgct tagttggtga tgaacctaga caaaaggttt ggagtgcaaa 16680 ggaaacgtag cgaaaggcac tacaaatgcc tgaaaagcaa atcaatatgt cagatgctca 16740 atatattctg agcacaaaat gaattctggt gccatttctt caaattaagg tttcaagcca 16800 tggcaattta tggttttact tttgaaagat taaaagcaat tgcactcatc aaatagaact 16860 taatttttaa ccatagcacc ttcgggtgct ttttttgcga gaagaaaatg ccaagcccta 16920 ttatccaata tttccaatat gaacatttac ctgaacattt gcagcaagtt agtaagccaa 16980 ttggtgattt agctcggcaa atggatgagc aacttcctga cgggcctgaa aaatccacag 17040 gattaagaaa gctacttgaa gcaaaagatg catttgtacg ccaagcttta agtaaataat 17100 catttataga aatgaagcgt cctaaagggc gcttttttat tgcctgccga aagcggatgc 17160 taacggcgaa tccgggcgga tgcccatttt gtatatatag gttggatgac caatgaaact 17220 taaaacagta acaatcgacg gtaaagttta tgcggaagta gacggtgata agccgatcta 17280 tattcatgat gacggcaaag aaatgccaca tgatgcacca cactcggtag caacaattgc 17340 acgcttaaac aatgaagcta aaacacatcg tgaagccaaa gaagcagccg aaaaagcatt 17400 aaaagctttt gaaggaattg aagacccagc ggcagctaaa aaggcattac aaacaatcca 17460 aaatctcgat gataaaaagc tggtggatgc cggtgaagtt gagaaagtta aagctgaagc 17520 tatcaaagca gttgaggaaa aatatgcccc gattgttgcg caacgtgatg ctctagaagc 17580 ctctttacat aaagaactta tcggcggtgg ttttgctcgt tctaagtaca ttcaagacaa 17640 cattgcagta cctgtggaca tggttcaggc aacctttggt catcacttca aaatcgaaga 17700 aggcaaggtg gttgcatatg atccgaacgg cgaaaagatt tattcacgtg tccgcccggg 17760 tgaacttgca aatgttgatg aagctttaga gtcattggtt ggtggatacc agcataaaga 17820 cttaattctt aaaggtggta aaggaactgg tggcggtttt caaggtgggg gcaaaggtgg 17880 agcacctact ggaatgaaac gcagtgaaat gtctgtttct cagaaagcag attacatcaa 17940 agaacatggc aatgatgcct tcctaaaact accgaactaa tcattaaata tttggagata 18000 agtagttatg actacgacag ttaattcaga catgatcatc tacaaccaac tggctcaaac 18060 agcctattta gaacgattac aagacaattt gaatgttttt aatgaagctt ccaatggtgc 18120 gattatttat cgtaatgaaa tcattcaagg tgacttcaat aaaaatgcat tctacaaagt 18180 tggtggtagc attaaacatc gcgatgtgaa ctccaatgca aaagtaactc cggaaaaaat 18240 cggtgcaggt gagtctgtag gtgtaaaaat tccatataaa tatggtcctt atgcatcaac 18300 tgaagaggca tttaagcgcc gtgctcgtac accagaagaa tttgctatgg ttgttggtta 18360 cgatcttgca gatgcattgg ttgcaggccg attagagtac agtttagctt ctttaaaagc 18420 tgctatttct agtaatcccg atatggttgc gaaaggaagt atcgttgttg atggccgcaa 18480 agcattaact cgtggtatgc gaaagtttgg tgataagttt ggccgaattg gcttatgggt 18540 gatgaactca gatacatatt tcgatattgt cgatgatgct atcactaagc aaatttacgg 18600 tgaatctgaa atcgttatct atggtggttt accaggaacc ttaggaaagc cggtattggt 18660 gacggatgct gtaggtgata acgatgcttt tggcttgcag tatggtgctg taacagtaac 18720 tgaatcacaa gtaccgggct tccgagctta tgacatcaat gatgaagaaa acttagcaat 18780 cggtatgcgt gctgaaggtg catttaacct agatattctt ggttatagtt gggatacatc 18840 gaaaggtgaa aatcctgacc ttacattact tggttcaagc gctaactgga ttaaatatgc 18900 aaccagcaac aaaatgacag caggtacctt acttgattta tcaggtacag cgacaactgg 18960 ttaaaaccta aaaattaaaa cctaaggggg ctaataagcc ctctttttat tattaagaga 19020 aaagcgccat gaagattatc tatacacgca ttgcagcagc tgctgcatta gagacgggca 19080 ttattgctaa ccctgactat tatgaaaacc caaatttgaa agcaaaagag gtaattattt 19140 acggtaatta tccaaagatt caaaaggatt acgaatcttt agaagttcca gttgaagttc 19200 gtaagttgga agagccacaa aaaacgactt tggccacggt aaatgtcgag gtaggagtca 19260 cccctgaact tcaaactgtg attgatgatg caaaagctga gtgtgaaaag gtagttgaag 19320 aaaacactca gcttaagcag aaaattgcca tcttagagca ggccggcggc aaccagtcag 19380 agttgttatc tgagaattca cgattaaaag atgcagcagt cttagcagat aaagctctca 19440 aagatgctga agctcaagtg gtcggtataa aaactgaatt tgaagctttt aaaaacgata 19500 ttcccgcaat gcaagcacgt attgttgaat tggaagctgg aaaatcggca gaaaacccag 19560 ctacagaaac ggcagctaat gattttgaaa actggtcaaa tgatcaatta aaagagtatt 19620 tggctagtaa aaatattggt tacaagccgt cagcaacaaa agcagaactt cttaaattaa 19680 tccctaagga ataatgcaat gagctttatt actgtagatg acgcaaattc aattttgggc 19740 agcgattttg caccagacag tgataaagct cgtctggtta aactggcaaa tgtctggatg 19800 aaaaacagaa taggttttgt accagatcct attgacccac ttcttaagga tgcagcttgt 19860 gaaattatca aaggaattct ggccaaggta atttataacg gcaaagatca gcagctgaag 19920 cgcaagaaag ttaaagctga ttctgtagag tcagaaaaag aataccaaga tggatctgaa 19980 gcaatttcta gctttgaaca gatagcaatt gattttattg attcacttga tttgaaagat 20040 ccaaatgcaa gttttaatgg ctttggcata ccactttaca gggcttgata tgggcttacg 20100 tgacgaaatt caggcagaca ttgctgaagc atttaatgat gatttggctg acgccgttca 20160 ttcatttact tgtgagcgga tctcaaaaac taattgggat cctaaaactg aaacatatgt 20220 tgaagttaaa gaaaactatt ccggccgagg cgttctgttt ggctcataca gtcaatatga 20280 gattcagacg cttggagtat tagcaacgga taagaaggcg accttgctgc aaaatgaagt 20340 atccatgaca cctaaaattg atgatgaatg gctaacagct ttaggttcat ttcgagttat 20400 ccatattcaa caagatccag ccagtacaat ctggaaatgt cagcttcgaa aagtgtaggg 20460 gctaaaatgg ttaatcctga ttatgttcct gaatggtata tctcgccttt tcaacatgtg 20520 cagtacacgc ttgctcgaaa tcaactacac atggatttgt tatttgaaga tatggataag 20580 gccgatcaat ttttggatat gggagcggat gcgcaagtta gtactttttc tgatggtgca 20640 tatgcaatcg tccaaattgg tgatacggcg gataaagacc gaattcaagt ttatggattg 20700 cttttacatg aagctgttca tatctggcaa atagtaaaac ggagaatggg tgaacgagag 20760 cctagtgtgg aatttgaagc ttattcaatt caggcaatcg ctcaagaact tttcgaaatg 20820 tacgaagcaa gcgaggtgag caatgggatg gaaggggaaa aagccgtcta gttttagtct 20880 tgatgtgtct aaagcagcag aagaccatgt gaagcatatt gttatggata ctgtgcaatc 20940 tttagttaat ttaagtcccg tcgatactgg tgcataccgt gcttcacata tggtttcggt 21000 tggatctggt gactatggca tacgtggacc tgaaacaaat gctattcagg atgcagctat 21060 tcaagccgtg aagtttaagt tgggcaattt agtttatatc cagaacaacc agccttatgc 21120 agagcgctta gaaaatgggt ggtctgatca agcaccacaa ggaatttaca acaccacctt 21180 tacctttatt tctcagaagt atggcggcta aaatggcaat gactttagag cagacaaggc 21240 aagctattat cgatcgtatg caagctttta ccggtattac gcaagacaga atccagtatc 21300 caaatttacc aggctttaat gtacctaaag atggtgtttg gtgctgctta acgattgcag 21360 gtggtcccag ttttacttct ggcattgcag ataagccatg tactcgccgt accggtaata 21420 tcatgattca atgctttgca cgtcccaatt caggaataat tgaaatcaca aaattgagtg 21480 atgcattact tgcccatttt gaatatttca caatcgaaca cttagaatgt ttgaatggtc 21540 aatccatcta tgcgggtaaa gatgctgatt tcattcagta taatgtgagc attgggtaca 21600 aggtgaattg atatgtcatg tatgctgact ttagaagaaa tcgaaattaa acggcaagag 21660 ctggaaagac atcttgaaga tgttatggct gttgaactga agaagtggca aagcgaaaat 21720 aagctatgtg tttccgatgt gaatatacgc ttggctaatg ttgattgtct cggagggcct 21780 aaacataacg ttgttactgg agtaagtgtt gatttagatt acaaacctta aattacttta 21840 attaaatgac cgctaagaag cagtttttta cgtctttcta ctaccacctc atcggtggtt 21900 tttttatgtc tataggaatc acttatgagc aattttgttt ttaagcgtgg tgacacattc 21960 aacttgaact tgcagctggt tgatatggat gaaaccctgc agtatccacc ggatgatgtt 22020 cgccgtgcaa ttgatctaac cggttacacc tttacttcac agattaaagc tttggctgat 22080 ggagcagctg tagctacctt gacttgtgct gcattaaatc aaagtacaca gaagggatgg 22140 ctgaatatta aatctagtgc aagcactgca acttggcctt tagggctgtg tcagatggat 22200 attaaagctg tagttagtgg tactacgcag cacactgaaa ctttgacttt ccaagtgatt 22260 gacggggtaa cagcataatg gcaaatcttg tttttaaatt tagttgggat caccggccat 22320 tcccgtataa ctcggctcag ggaaaacggc aattcatgct gccattcgct tcaggcattc 22380 ctaatctggc accaaacttt tcgcaggtcc aaggtactgc tgcagtctct caaggtggta 22440 ctggggcaac cactgcagca gaagcgcgaa ataatcttgg tgctgctgaa aaaggtgtaa 22500 atactgacat tactgaaatg aaaggtttag ctactccact ttcagttgcg caaggtggaa 22560 cgggtgcttc ttctacagca ggtgctcgtt tagttcttgg tttaggtgat atagggactt 22620 ctggattttt tggaagtaaa attagcgagc tatataacaa ggtgtcggtt ccacaatgga 22680 tagctgtatt aggtgataac aagttcactt tcctatcaag tggcgactgg caagcgggga 22740 atacaaagaa cccacttaat atgcctagcc gatatggttc tttaatgtcg tatttgggat 22800 caagctcata tggaacgtat tcatggcaga tttttaaggc agtattgggt ggacagcttt 22860 cctaccgata tggggcagga aataatgtct ggactacatg gggacacatt aaaaccagct 22920 ttaatacatc agtcgatgca aatgggttct taaaatcggc atcaccagta gtgaagttat 22980 ttaatgatca tattgaactt aatagtgatg cagaaaagca accaatcgaa tttaagaaag 23040 ttgatgtagg cgattattta cttaaaggct ctttaggctt tgctcaagaa ggttggtata 23100 tcgaagcacc taaagacgca aacggcaaca caatcgttgc agtagtgtat gacaccctag 23160 aaaatggtga catctcaatt aaaacttaca agcgtaagtt tgattttgaa cttgctgctg 23220 ttgtggcaga tcacgagaac ccaatggaca ttccagaagg ccgctggatt gatatccgtc 23280 tgcatgaaga acctgaacca gaacctgagg ttgaagaaac tttgagtgaa acaccagtgg 23340 atttccagcc gactaactta tctcaggcag ttgctgcagc catgaatggc gtggaaccgc 23400 cagaaatctc agacacagac gaaacacttt aataacccgc ttaaaaagcg ggttttttat 23460 tgcctaaatt ttggagaacc ataaatgagt tcaggcgcaa aaattcgatt atatgcttgt 23520 gaagaagcag ttttaggaac aactcctgca aatccagtct ggtacaccgt tcgccgtgtt 23580 actgatagtt tgactgaaaa tgttactact gaagatagca gtgaagtagt tgattcacgt 23640 tttcgccaag gcgctgttgt aacggaagcc gaagtaactg gtcaactaga gtttgaatta 23700 tcactaggta cctttgactt attcttaaat gttctcgctt tcaataactg ggctgcaaat 23760 gctttaagtt ttggtggtgg agtacgtaag tctcttacct tggtaaaagt ctttgaagat 23820 attggtcaag tctttattta tcgtggtatt caagtgaata caggtgaaat gacgatccag 23880 accacaggca aaatcactgg taactttggt ttagtaggta gctcatttac gcgacagcag 23940 gttaatcctg ttacaaatcc tattccagca tcgactcgcc ctctggtgag tatgccaaat 24000 gttgaaaagc tacttattaa tggtcaatca attcagggta aagcttgtct gcagacactt 24060 accatcaact ttagtaataa tctggaagcg atccgttgta tcggttctgg taagtacacg 24120 cctgagtttt acttagagaa aatgatggat attggcgtaa atgctaattt catgttttca 24180 gcaacatctg cttcttggat tgatgctatt aaaacccgtg atgtatttac attgaccttc 24240 gatattacag ataccaaagg cagtaagtac tcgtttaact tcccgcaact tgaagttaag 24300 gaagcaaatc accctgatgg tggtggcgat gacattatta caatagatat caattttgcc 24360 caagtgcgta ccagtccaac gattgtacgt gctcttgtgt aatcaactta ttcagtaaca 24420 aagcctatgg aaacccatgg gcttttttat ttctaaaaat tagaggttgt tatggcttta 24480 aaagtcggaa ttattaaaag ctcggacgta tcaaaatggt gtgaatacaa gggggttgat 24540 ggcgaagtac aggcagagtt caaagtccgt ggtatcgcct ataaaccttt tcaggtagca 24600 attgaacgag ccggaaatca gatttcatcc aaaggctatg atgtgatggt caaagatgaa 24660 aatgccaagc tttaccatga attgttaatg gatgcgtgtg ctgcccactt aattgaagac 24720 tggaaaggtg tggtatttgc cgaaatcgta gacggtaaaa cggttgaatc tgaaaagcca 24780 tatacacctg agaatgcctc aaagcttctt aatcttggtg atattggtat ttcaatctgg 24840 ctattcatta aagaacaggc tcagaggatt caggaagaag ccgacaagga taaggcttta 24900 attctgggaa agtcgtcgag ctctacaaat accaaaaaac gtatgcgtcg aaaacgccgc 24960 acgaaatcga gcaaatcaag ttcttaggtg gccgtattcc ggatccgcca gaatattcgt 25020 atgcggccga ctctattctt tcggcattta gtactattgc cagatccaga cggtatgagc 25080 agggtatccc gttatcttta gatcagcagg caatcaatgt ctatgcagag cataatgatt 25140 tacccgtggc tgctcatatt tttaatgact gtatttttgc tttggataac ctgtttctgg 25200 atgagtgcca taagaagttt aaggcaaaaa aataaaatgt tttaaagctt tattccttaa 25260 agcttaatca agtgcgggat attttaagaa ataaactata taccgcactt ttagcatagt 25320 atttctaaaa tccttaatag caagtttgtt aagttgttga attttaatat tttaaatttc 25380 aaggctaggt gtttaagaat gtaatttcta gttgacataa atgtcattaa gaaatattat 25440 attttcaata gtaaattata tcgtacgaaa tattgttgaa tcgcacgatt actattaatg 25500 ttaattttat ttaactgatt atcttattct attttggaaa ttattatgaa agctccagca 25560 atgttggtaa caccaacttt tggtgttgat tcatctcaaa aaattcttca agaagctcag 25620 aaaaaaatta cgccagctcg taaatcacgc cttgagcagc ttgctcaaat agcaaaaaac 25680 gcatttaaaa attaattatg aggtttcaat ttgtccacag agattaatat ttctgaggtc 25740 gagttacgaa atttagattc agtagaaaag catctttatc aagatttttg ttgtgagcgt 25800 gaagagctca atacgttctt gattgaagat gcttttgatt atcataatta tggtttaacc 25860 cgaactactt tggtatttca taacgatgta ctgattggct attttagctt gtcagctgat 25920 aaaattgtgc tcactcaaac agaaattgat gaattatctt taaatgggga atttaaagta 25980 acttatttcc ctgcagtaaa gattacaaaa cttgctattc agaaagcttt tgctggcaag 26040 gggtatggta ggcttatttt ggaattaatt gaaggcctag tgtatggtca acatatggct 26100 ataagatttt tgactttaga tgctgtaaat gaggaaaaag ttcttaagtt ttatgagcga 26160 aatggattta atgaaagtct ccatgaagct agacagcaaa gacaaaagca aaataggcaa 26220 acgatattaa tgcataaaga tatctttagt gaataaacca ccttcgggtg gttttccttt 26280 atgtgacatt taatgatcag tttgctaaat tacccccaaa tatgagggta tttttatgct 26340 taaggactat cttgggcctg ccgctgaaca taagcacaaa gcagaacaag ccattaaaga 26400 aaagagattt gatgatgctt ggcgtcatct taatgagcaa aaaataaatt attttcagca 26460 cgcaaaacaa tgtaatttta ctgaaaagca aactttgggg cttgatgcgg ttgtgcacat 26520 cacaatgggc aatttactga gaagagaagg taagcattta caagctttgt atcacattgc 26580 ttatgtttat aaggtaggta agctagagaa cccccaaaat gacagtaacg atgataggct 26640 aagaatctac tataaaagag caaagaaaga tggtggattc gagaacttta aacaagggct 26700 tgaccttttt cccagttatg attatcagtc agtgcaacat ttcacaagca gccttttaaa 26760 ttctggagac gtaaaacaag gagctattac ttctcctcaa attgaggaaa agcctattac 26820 aaaaatccca gaaattaata agaacgctat aaataataag tttttggctg aacgcaagaa 26880 aaaaaaggaa gaacatattg ggattcctcc tccattaaaa aagcccgaga agaagcaagt 26940 tattcaatat gaaaagacga atagccaaat aagtgcaaca cctgttagca gtagttcaaa 27000 aactgaagga tgtaggagtt cggtttcagg gttctttatt gcagcgactt gcgtggtgat 27060 aggtttaatt ctgcttgttt ggttgctttc atactaaaat agtaaactag agaataaaca 27120 cgctacatgt taaattttac tcaaagataa tggtttggga atatgaaaaa gattatttta 27180 ttaggtttaa tattaggttt agcagggtgt atgtctactg ctaatttttt tgaagtgcaa 27240 gccacctctg ttcagaatag cggttattgg accgggcaat atgatcgatt agtaggaaca 27300 ttaaagttaa attccgatgg aactggtgtt atttgtcagg atggaatggg aacagcgaga 27360 gtaatgtctg ttaaaaaatc aaatgataaa ctctattcac aggatggcag cttctggaaa 27420 gtgcaaaatg aaacactcaa ctctatgaaa ttaaattatg caattggtgg tggttatgaa 27480 atgaaaaaag atgatgattt atctttggca acaccagcat gtaaagaaaa attgaaatga 27540 attcaaaatg atttgttaaa aatttgactt agatcaggtt ttttattttt gattaatgac 27600 cgccttttgg cggtttttta ttgcctagag gaaagtaaag atggcacaag aatcccgttt 27660 ggtcattgtt attgattcgc aaaatgctga acgtaatgcg cgtaatctag gcaatgagct 27720 caatagcatt gagcgtaaag gtgaatttgc atctaagtct atggacagct tgtctgtagc 27780 caccagagct ttagctggac acatggctgg tttattaaca gtaggttcag ccatttcaaa 27840 gatggataca tatactggat tacaaaatcg ccttaagtta gtcactaaca atcaagttga 27900 actaaataaa gcaacggaag acactttccg aattgctcaa aaaacctatt cagcatggga 27960 ttctgttcta caggtctacc agcgttttag tgataatgcc aaaactttaa acctcacaat 28020 ggatgacact gctcgactaa ctgaaacagt atcaaaagca gttgcgatca gtggtgcaag 28080 cgcagaagct gctgatgcag ctttagtaca atttgggcag gctttggcaa gcggtacatt 28140 acgtggtgaa gaactcaact cagttatgga acaaacacca gctctagcaa aggctattgc 28200 tcaaggcatg gggatcaccg taggagagtt gcgttcagtt gcggctgaag gaaaaattac 28260 ttcacaagaa atcgttaaag cgcttaaaaa tgtccaagat gaagttgatg ctctttttgc 28320 taaaactgac attacaattg gtcaatcatt aactctactt aataatgaaa ttactaaatt 28380 tgtaggagag gctggtaaag gaagcggagc agcacaggct ttatcaggat cgattcagtt 28440 attagcaaat aatttgaatt taattgcaga cagtgcattt gccataggta ttggcttaat 28500 gacaaaagcc gttttaacaa aaacggttgc tgtacaagcg agcattgctg cgtcaaccaa 28560 acaagtgttt gccacaattg ctgaacgtaa tgcaaatatt gcagcagcaa aagctgaagt 28620 ggaatctgcg cttgccgaag cacaaagtac acaggtgaca ctaacgaaca tcaaagctac 28680 tcatgctcag atcatggcag aaatagaact cgaaaaagtt cgtttaaaag cccaaatcac 28740 tgaacaaggt cgcacggcta ccatcacacg aatggctcag cttggacgat tacaagctca 28800 agttgcgtta gaggttgctg ctgcggaaac agcacagtct gcagcttcat ctagattatc 28860 agcagcctta acagcgcaat ctgttgctac tagccgttta gctttagcaa agtcagcgct 28920 tatggcgatt tttagcccaa tgggtttagc aattgcagca acagccgcat ctttctattt 28980 actaagcagc agttcggatg aagtcaaaga gtctcttgca acacaatctg actcggttag 29040 tgatttaaca gataagtaca taaagttaaa tactgtgcaa gcattaacag agggtgtgcg 29100 gttacgcaaa gagattgagc agcaaaatga tgcaattgat gatgctagtg gagctatcaa 29160 acgttttgct tatatccaaa aggaattatt taaattatct ggcagtgatt atgaagatta 29220 tcaaaatgcc attaagtcta ttgctacagg tgcaagcgat gcaggtgatc tcttaaaaaa 29280 gatgatttca tctggtcgtt ttagtcagac tcaaattgat aaacttattg agttctctag 29340 tgtagtagca gaatcaaaaa ataagattga gcagggtaat actgctctaa aactcttaaa 29400 tgctacttct ggacaacatg ttgaggtaac ggccgaatca attaagcaat taactattca 29460 aaccaactta acaaaagttg ctactcaaaa tttcactgac atgaaaacac aaatgcttga 29520 ttcattacga gcacaagtgg aattcattcg gttaaatggt ggtagcgaag aacaagttaa 29580 atcgttgaat aaggtaatcc aggcatattc tttaaatcaa atttcagcaa ctgatgctgt 29640 ggacaagttc aacagtactg ccaaagttcc tgctgaaaat atcaaggggt tacaggatta 29700 tgctactaaa acggatcagt ctaaaattgc gttgaatcag gctaatgctg agctgaagaa 29760 acaaaacgac ttacgtaatg agtacctaaa acaacatcaa actgtacttg gtgctcaaca 29820 aggagaaaca aatgaattaa ataaccaagt cgctgcacaa gaaaagttaa ataagttacg 29880 agacaacgcc aacaaagata ttctgaaaaa tgattttctt ataaaaaaca ctaaggcatt 29940 tggtggtggc gaaaagggtc ttgataaggc gcgtgcggca tcagagtttt ataccgacaa 30000 taaaattccg atgactagaa gtttaactag tcaggaagct gcaatttttg aggcttggta 30060 taagaagcag aaggaagcca aggacttaca agaaagtatt accgaatcta gcagaaagca 30120 aacaaaagag gttgaaaaac aaaccaaaga gtctgccaaa caagctgttc tacttgctgg 30180 aaatgatgag cgagtgagaa atatgctacg agtgtatctg gcatttcgaa atgcaggttt 30240 aggcgataaa caagctcgtg taatgacagc tcaagttgga cgagagactg attttagaaa 30300 tgaggcaatg tttggtagcc ataaggatga aaataatggt tatacaaata ctggattttt 30360 atcatggcaa aaaagtcgct caactaaatt aatgcagtct ttacaagggc aaggagtctt 30420 ggataaaaac ggtaaaatcc agcaaactca agatgcatta gatgcaatgg ctaaacacgc 30480 tgtgcaagag gcgatgaccg ataaaagtta tagtaaatct aaagcagctc ttcttaatga 30540 cgatttagac tatcgaagtt tagagagaat tgttgccaaa aattttgttg gctgggacta 30600 tgacgggaaa aagcttggca aagctaaagc ttcacagcat ttagccaaac aagactctta 30660 ctataatcag cttagtaaaa ttttagggga taaccccgaa gcagcctcaa aagcaattag 30720 tgatctttcg aaattcgaag atgaagcata taaggcacgt gcaaaaactc ttgaggaaat 30780 taagcagctc caagcaacat atgattcaga aacagttgct agaagcaaaa aacgtgagga 30840 ggaaatcaac aaagcaacca ttttaggtca atcaaattta atcccaaaaa ttaatgagcg 30900 ttatgatgct gaagataagt tagctcagaa gcaatttgat tttgaagtaa atggttataa 30960 gtggactgag aagcaaaagc ttgagtacac atatgaaatc aattctttgc gattagttgc 31020 tgaaggcaaa ctctctgaag atcaaagaaa ggttgcttta gatggcctgg aattgcaaaa 31080 gcagcaagag ttaggattac taaaacttgc tcaggaacag cggttgtttc aggctgagca 31140 attcatgctg ggagaaatgg agcgtatcaa aaaacgttat gcgcttgagt atgatgaaat 31200 atcaaaaatc actgatcttg aagagcgtag aaggaagatg agtgcatttc aggctgattt 31260 tattcgtaat ggtgtgggga atccaacaat tgatcagtat gatacctcta gtcagtttct 31320 taaatcgaca aactacacca agcccaagca aaccaatatg caagtattgg atgaagatta 31380 cgctcaaact tatcaaaagt tgaaagataa tcttgcagct gttttggagt ctgaaaaagc 31440 tagttatcag gaacgattgg aggcggagcg cgtattcaaa gaagcaagac agcaaatgga 31500 taatgagtac cacctgaagg cgattgatgc aagaaaagca gatcacgaca gtcaattgca 31560 attatacagt cagatgattt catctgcttc aagcacatgg ggaggtttaa ctcaaattgt 31620 taaggatgcg cgtggtgaaa attcacgctc tttcaaggca atgtttatag ctcaacaatc 31680 ctttgctatt gcttctgcga ttatctctgc tcatttggca gctacacaag tagctgctga 31740 tgcaacgatc ccattttttg gggcaaaaat tgcggcttca accgccatgc ttgctatggg 31800 atatgcaaat gctggtttga ttgctgggca aacaatagct ggattctcag atggtggtta 31860 cactggatct ggtagaaaat atgaacctgc aggtattgtc cataaaggag aggtggtatg 31920 gtcccaagag gatattaaac gctggggcgg agttggttta gttgagaaaa tgcgtaagag 31980 tgcaaaccct gaagcttttc tcaataacaa tgcctcggca gatagtgtca tgcgccgtgc 32040 aatgatgagt tctaatgcct ttatagaaag ccaaaagcag gctgacatct ttaatcaacc 32100 agttcaagat actcagatta tctataaggg taatagagac acacctaagt tagcttcttc 32160 ggcaaattct gacctgttcc atgatggcaa ggtctacttc tcatccaatg gtatagttca 32220 ggatcgctca aatctggatg atgttcagga ctttacttta ggacgtactt cacgccctca 32280 agctgagatt atgccttcaa ttgagcaatc ctctccaact atcaatttca agattgaagt 32340 cgtgaatcaa gtcagtggtg caactgttga agctgaacaa ttggatgaga aaactgtccg 32400 gatcattgtt acagatgaac tggataagca gcttccaaga aaggtaccta agcttgtaag 32460 tgatcaaatc gcaaatccaa actcaaccat tagtcggtct ttgactgaga atacgacagc 32520 aagacggaat cgataatgaa caaaaccgcc ttcgggggcg gttttttcaa actttttaag 32580 attcaaaaat cttcgtaata cttagaatga ttctgagaga aatgattaat ttcatgtatc 32640 ttataaaata aattcagtaa gattgtagat atatctttta tctttattaa gacatgaaaa 32700 caccaattcc aaaaaccaaa atggatgagt taggttcgct gataaacggc ttcaagcctt 32760 ttgaagtcct tagtgagttt aattatgtaa ggtgtatgcg gttacttgat agtagtaaac 32820 agactgcacc taaggatctt tggcatgtta tgaaagggct tatagagtta aatgctaata 32880 atttaagtga agcaaatgag gcagcattat atgttttaaa acattccaat aattttagtt 32940 gtttaaggaa tgcaatttat atttttaatc atacttttga ttttgataat gtatgtaaaa 33000 caacagataa aattgtaaag ctaattgaat tacaaaaaat ggattccaaa ggaatcttac 33060 caagagatct tggacttatt ttcttactta atggtgagtt atgggctaag gactcatcat 33120 tttatagtga agctgtgttt aataacagtt ttgatcatca cactgtactg gctgatatca 33180 atgatcgact agatataagt gaaaatgatt tcaaaaagat ctcttctatt atcaagaata 33240 ccgttttaaa gaataatgcg agagtactca accatgacta tagctttatt gatgaagaat 33300 ttttattact tatatatata aataaacctg taaaagagat catgaaaatt aacgaggaaa 33360 ttattgaatt atgttttaaa gaaggtcttt tgactgcatt taacaagatc tcatatacat 33420 tcgttcctta tagtgaggtt ctgaatggat aataagcttt tagaatattg taatgaaata 33480 gcatctgctg aaacctcata cccagattta caattaagaa atgttatcgg tagagcttat 33540 tacttcacat ttcatgaagc aaaatatcat cttgaagata gattgaggtg gaagccaact 33600 tcagaaaaag gtggggttca tgcaaggtta tatagcagtc ttctcagtta tgattcaaat 33660 gctaatgaac aaactaaaat aaatgcagag ctagtttatg caaagatcaa ttctttaaaa 33720 aaattaagaa ctagggctga ctataaaatg gaaataaaga ttacgcgcga acttgcaaat 33780 tttagtattg aagaagctaa aagaatttct gagttatttg aactaattta atttacaaca 33840 tttgaaaaaa ccgaccttaa atggtcggtt ttttattacc tgaaggaaag ttatgtacaa 33900 gttaaagcta aatcctcaga ccagcggcta tggcgtaaca ccgggtgatg atgtgaaacg 33960 tcagcagatg gatggcggac gtggtcgcta ttacatcgat gtaaaacgta atagtcatat 34020 tgtcgatgtg aactggaatt taagtaaaac cgatttcaat aaaatgatgg ctttctggcg 34080 gatctatcag aataagccag cttcattcta tgcggatttg gtcatagacc aaggaacacg 34140 tcagcaatac caatgcaatt tcattccgaa ctcgttcaag accaatgaag tgaatggcaa 34200 cctttaccgg gtaaatgcac agctcgaagt tgttcaaaac cagcctaacc ttacggccga 34260 tatagctttg attaaggatt gggaggtcta atggataacg aatacgccaa gttctttttc 34320 aatcgtaaag tcgatgttta tcaactggaa tgtattgagc tttctcatcc ttcctttatg 34380 aacatatacc gaatagttcg taatgatgat cgtggggtgt atgtacaaca taaggaagga 34440 tccggtcagg tctattatga atttttgcca gcatctattc aaagatccgg aatgctgggt 34500 gatctggacc agacattaac cgtttctatc tctggtctag gtgatgtgat gccagatgag 34560 tttgaacggg taatcgaagg gcaatatcca gatgtaaagc caaccgtaaa ttaccggatt 34620 tacagttcag acaatctgaa ctctccaatg ttttatttac ttggactgca actctccagt 34680 gttgccatga accataaagc tgtgacgttc aaagctgaat ctccacgatt aaataccgct 34740 aaaactggag atatctttgc actagaccgc tttactggtc tcaagggggc tatatgaaaa 34800 gtcatgatca tttgcttgat agacaatatg acgaggaaaa ctacaactgt gttcattttg 34860 ctcatgaagc tgcattggat ctatatggaa tagaccgggt ggaagcactt gaatttttta 34920 tgaagcctat taaagaaaag gtatttctac catcaaggtt aaaactttta aatccactgc 34980 ccatgcccaa ggaaggctgc atagtcgcct ttcactcgag ataccgaaac aagcccccac 35040 atgtggggct ttttcgtttg gggcgtattt tgcatttgca ggaatcaggc gtttcatgga 35100 tgccaattca agtcgttcaa gcatttggat ttaatcgtgt gagtttctat gattaagatt 35160 atttataaac aagacccttt atccgaagac aaaacaattg aacacgccga aactttgggt 35220 caatggctta cttcaaaata tgattatatg cctgaacatg tccgtatttt ccatacaaca 35280 agtaatatgg atcatgccga aatttcattt gcgaatgaag tcacaccgaa gaatgcatat 35340 gaattaaagc agctcgattt cttgccaggc actttcattg taattgagaa tcccaagggt 35400 atagacccca taactctagc ttggatagcg gttgcttcta tagttatggg tgtggctgtt 35460 gcattattaa tgcctgtgcc ctcaattacc caaaccaacc agaataacaa tcaatcctcg 35520 tctgcaaata acgaattatc aaaccgtgaa aataaaactc gcgtaaatgg tcgtatcgca 35580 gatatttatg gtgccgctca cgatacccct gatctgatta ctgtgcctta caaggtatat 35640 gaaaacaatg tcgaagtaga gcatgttgtt ggttgtattg gtcgtggtca ctataaaatt 35700 aacggtgcat atgatggtga aaccaacatt gttgatattg ccggcgcatc ggtagaagtc 35760 tttcgaccag gtgtagatat tgtttcaggt gagccatatt tttcgcttgg taccgaaatt 35820 accacgccgc cactaacggt tcagcatcaa acttctgtta atggccaagt tctccgtcca 35880 gcagatacac agtctttaga aggtacgaac taccttcatt ttgcatatcc aaacgagatc 35940 cttcgggcat ctgcaaacaa tacggattta accactaagt ttgtaagtaa tgaccgcgta 36000 gaaatcacca atgcctcatt cacgtttaac ggccagactt atgatttaaa cggcacttac 36060 agcgttctat cggtagcaga tgatcgaatg acgttatcaa atccggcggc cgttaatgct 36120 aactggttaa agcttaaaga gttaaataac caacaaactg cagctttgtc accaaagatc 36180 agttcaatag gtgaaaaatg gattggtcca ttcattctgg acaatgttga acgtagccgg 36240 gtgctgtgta attttgtggc cacaaatgga ctttataccg tttcttcagg tgggaatcag 36300 gccgctgtta acgtcacgat tgaagttgaa gtaacaccgg taaatgaatc tggtgcagcg 36360 attggtaatc cgatgctgaa gcagatcatt ttgaaaggtt cggcaaagtc gcgtcaaacc 36420 gttggcgcaa cgctggatat ggtgacattt caaggtcgct gtagtgtccg tgcacgtcgt 36480 ttaacaccaa caccggcggt tacaacggta gtagatgaag taaagtggca ggcgctttat 36540 ggtgcttatc ctttgcaaag cacagtgtat gaacatgaaa cggtttttcg tgcgcgcact 36600 tatgcaacca ctggagcttt atctgttaag tcccgcaaga tcaattttga tcttcagcgg 36660 atgttaccga cttttaaaaa cggcgcaatg acgacagagc tatttccaac atcaagcttt 36720 gctgatgcat tggtttcaat ggcactggat gacaagatag gccgccgtac gatcgacgaa 36780 atagatctgg aaaatatcta tcggacttat aacgatgtag ttgattattt tggtacacca 36840 cttgcggctg agttctgtac tacgattgat gatacaaacc tgtcttttga agagctggtc 36900 accaatcttt gtgatgccgt gttttgtact gcatatcgtc aaaataataa gctcaagctt 36960 tattttgaac gtccaactga taactcggta atgctattta acttcaggaa tattattcct 37020 gatagttaca agcatgatct tacctttggc gtgatggatg actacgatgg actgatctat 37080 gaatacacgg atccggccga cgatagtcgt atcaatatct atctaccgga taaaggggcc 37140 aagaacccca aagaggtgaa atctgtaggt gtgcgtaaca agtggcaagc tcattttaat 37200 gcgtaccggc tttggaacaa gcttcgcttc cagcgcaaat ccattacctt tgatgcggca 37260 cctgagtcag aattactggt tttacgtgac cggatcgctg tagctgatta tcgcaatggt 37320 attcatcaaa gcggtgaggt ggtacagcaa gaaggtttaa ttctcaccct aagccatgat 37380 gtcgatttca ttgcaggcaa gagttatgtg atttatttgc aaatggggga tggtaccgtg 37440 gacctgattc ccgttacgcc gggttcagcc aagaacaaag tagttttagg gcgtttaccg 37500 aacggggcct taaagcttag tcccgatgac tttgtgaata ctatctacac cgtagttaat 37560 gacgatacca aaggctcact gccttatctg gttgcaaaaa gagaaccggc tgaccagttc 37620 tctaatacca ttactgcaat taattacgat gaacgttatt acctcaatga caaggacttt 37680 attgatgtgc cggttgatga ttcaccgatt tacattcgat atgaccagct ggatattaat 37740 ctggcacgtt tatatcagat gcaaagaggg gatttgccaa cgactggaga aatcagtttt 37800 gtagttgaag caggtgcact agtttcaagt tcaagttctt atcgaccgga aaccagattt 37860 gtctataaat tcgactataa ctctagtcct gcaaaacgag agtatatcgt tccagctgca 37920 tcagaattac ctgctattga tactggtgag ttcccacctg atctcgtggt aaatttgact 37980 attaaaggtg ctgttgttgg acgtggtgga gatggcgggt tgccacattt ggcatttggt 38040 gcatggtcta ccgatccgga ttataacttt actaaaaccc gccgtgacgg ttttcaggga 38100 gcacccggtt tattaaaccg gcacagtaaa ctaaacctga ttattgatgg tggaactctg 38160 gctcgaggcg gctcaggtgg tggagcaaca ccaagcggta tttatacagg attatcgtat 38220 ggagttcagg gtattcccgg tggagctgga gcaccttttg gtcgggttat gaccggacaa 38280 cctattacta acgattcaca agactggcgt tggtacttaa atggtgactt tatggttgtc 38340 aaagtaaccg atgccgaagc ttcggtaccc ggtaaaggtt accgaaccca aaatgatcga 38400 tatggatctc cattgtctgg tgatggtgga ggttggggcc agcgcggtac caagtccacc 38460 aatgatggaa catggaactg gcaataccat ggcacaactg aaggccagcc ggggccgggt 38520 ggacctgcaa ttgttggggt ggcaccactt acaactcaat tgatcaatgg agggaaaatt 38580 ctacaaacac tttaaatctt aaaagaactt tgagcaccca attcgggtgc ttttttattg 38640 cctaaatttt ctggagatat aaatggaacc agtttccaca agcggtttaa cagcaatttt 38700 aaaattttat ggagcggcaa tcatggtgac tttagcggtc gctttagttg cagcagtagt 38760 attaatgaca cgtatgccac gctcaccaca agagtgggca gtgggcttga tctgtacggt 38820 tgtatcaagt ttggctggcg gctcattcat tattgtgaag tgggggcttc atgaatgggt 38880 tactgatgta tgggggatga ttgctctagg tgggttcttc tttgtttgtg gattacccgg 38940 ttgggctttg gtccgttgga tttttaactt catagataaa caggaaggta aaacgattgt 39000 ggaagtgatc aaagagttta agaaagccag aaaagacatt gaaaacagtt aatgccgcct 39060 tcgggcggtt ttttattgcc taaaggaaac cgaaatgaac attgaaaaat atcttgatga 39120 attaattaag cgcgaaggtg gttacgtaaa taacccagca gaccgtggtg gtgcaactaa 39180 gtatggaatt actgaagcag ttgctcgagc aaatggattc aaaggtaata tgcgagattt 39240 acctctggat gtggccaaag caatttatcg caaaaactat tggacagccc cacgttttga 39300 tcaggtgaat atcatttctt ctgctgtagc tgaagagctt ctagacactg gtgtgaattg 39360 cggtaccgga tttgcaaaac ctcttttaca acgtgctttg aatctcctaa ataacaatgg 39420 taaagcaggg tggccagatt tatcagtaga tgggatatat ggtccggcaa ctcttaatgc 39480 actcaaaact tatttggtca aacgcgggaa agaaggagaa aaagttttag ttcgagttct 39540 gaatattatg caaggtcagc gttacattga aatctgtgag cgcaatccaa gccaagaaca 39600 atttttctat ggctggattg ctaatcgagt atcaatgtga agtacctaat tttactgtgc 39660 attctactca agactgcaca gttacttcga cgtatagtga ggtagttgta aaagtttata 39720 ggtaagttat aggattgatt ggtaataatc tttaaatttt agggggggga ttgttcagat 39780 gtagtgtatt ctgtaaaata aaacttaatt atattttgct ttcaatacaa tgaacgatca 39840 agttttccaa ttacaaattg ttataaatgg aggtttaacc cccattcaat ctaagccaga 39900 aacacttgat aaattagtaa aagaatttgc tataaatcat ttgttgtttc caaaagaaat 39960 aactgaacaa ttaattgaga ttaattctca ggatggttct caaacaaaaa agataactaa 40020 atttattgat ttggttagta gcaatcaaaa atgtacctac caaattagaa atgattcact 40080 tgtattttta aattcctttg agaaaataga ggaattagaa agtatatttg aaaagttttt 40140 taaatcgttt tcggatctga ccccatatat aaactataaa caatcaaaaa gattggggct 40200 agttcttatt agggaggatt ataatgaggt tacattacgc gagtattgta cttcagaaga 40260 attagatcga aatgttattg agaatagatc gagaaaagtt actcgttttg ctatggcgga 40320 actaaatgaa atggtaaatt tatctgtttc aaaagattat gtaactcatg aatcaggagt 40380 ttctcgaaat actctagcaa gtgtttatga tgttaatacg ttatctacta aggatgtttt 40440 tagatttaca agtaaggatg tagtaaagtt tataaatgct tcaaagaaat ttattttaga 40500 atcaatgtaa gattttttat atgaactatt caaataattt atctaataat actatgtatg 40560 aaagtggtaa tcataaaaag ataatcacta agtacgagat tgaaacaata aaaacggttt 40620 ggcaaaccga taagatacag tcttttttaa aagattactt aaatacagac gtagttagta 40680 ttactgaccc cactgttata gaacaaaaga taggggaaga gagcttaaag caaattaaaa 40740 gagaatttga tatttttaag aataaatttg ataattttct gagatatgaa gatgtgccag 40800 tcgattatgt ttcacctatt gaaaatgaat taatcaactt ttataaacat agtaaagttg 40860 aagttcaaga acaaattagc caatggatta ttgattcttt tgataacaca aaggttcttc 40920 ttaatatttt aaaaatttta ggtaatattg ctcctgattt tattgatcat caatttttaa 40980 ctaattttct tatcgttctt aatcataaag atactgaaat caaagaatat gcattaagaa 41040 ttcaagagaa attaatgctt ccatcatata ataatgtact gaagcactct aagttaactc 41100 caaaatggat tgatgactat agaaaagaat tggttgaatt gtatgaagaa gataataaag 41160 gtagttaatt taatatgact atttttgtaa gaaagataag taaagcaaaa tggccttctg 41220 aagaggaaat tgcagaaaaa gcactggatt cagaaattat accttttgtc agagccgatg 41280 ccttaactac ttgtttaaaa acttctcaaa atactttatc tgtttgggca gaaagattaa 41340 aagaaataaa ggcggtttaa ccgccttaaa ctgttgcaag ctgtgctgta ttaagcacag 41400 tcttgctttg ctcatatttc aaaacgtctt tctttttata tgaaacacgt ctcccaattt 41460 tcgagaaagg cagtgatgat tgatcacaac gcattctagc taatgtccaa ggcgagcaat 41520 ctaaataaag tgctacaacc tcttgaggaa acttctgttc ttcattagcc attatgaagc 41580 gatccaaata ttcttgttgc tctgcatcag atagatttct cagatctttt aacatttact 41640 cctccttact ttccgcttta acttctcgat caagacgctc aatctccgca attaataaag 41700 cggctgcacg aaccaaatct tgtcttgggc tttttggttt ccagaaagta tcagcaaaag 41760 gccaccatcc tgcagcatcc tcatccatat acacttcggg gccgaaatct ttgctgttat 41820 aaacccaacc tctacttact acatgatcaa cgtaacaaga tgcagctcgt ggcaattcat 41880 ttgcttcata gagattatca aattcaggta aatacccttc ttttataatt tggcgttctc 41940 tttcattaag aacatctttg acagcttgac tgctatataa ttcactcatc cctcagctcc 42000 cgattcgctt gccacttcaa ccatcaaaga ataaataggc gtgtaatgat cacgagtccc 42060 atcgccccaa tggaatccac tattttctaa acagctaaca acgctgtctg gaatctcttt 42120 cggcacaact acataaccct ctggcaccgc ctgagctttg gctttttcta gctctgcatc 42180 acgatgcttt gcacatctaa gccaagcatc ccaacggcta ttcatgttgc ttatttcttt 42240 ctgagcaatt tcagaaggat tgtttgatct agtcataaac agttcatgct catgactaaa 42300 aataatgtct cttcttcctt tgtaatattg gaaggtattc agaaaagcct ctctttcctt 42360 attcaaatca aacatcatta ggccctcaaa tattcttctt tagtccactc aacaaactct 42420 ttataaagct gctgcgcggg tttatttaac cggttgtgat agtcgatcgt tatgcggcgc 42480 caagcgactg gtaccgcata atgtttggtt agaaacattg cttgatccat gccttgccgg 42540 actattacgt agcccagcaa ttgcaagtag tacataaaac caagcatgtg tttttggctc 42600 actttcttgt actgatcttt catgttagaa accgtccact aataaataat cagggggaga 42660 ttcttgttga gtaggtgtag gattctctaa ttcatagcgg cgttttctca cataccccat 42720 tagcttcggt tgaatctgcg gatctcgtgc agccacgtct atttccaaag catctagcgt 42780 tgtaaggtct ggtgcagttt ggatttgaac cattaaagag ggtggctcat tagcagatgc 42840 cttttctttt tctagctctt caagacgttt gtgagtggcg agaaggatag gcttcatttg 42900 ttcgtcatcc catgtgcggg tataacgata aaccgcattt acttctgcag gtgtttttga 42960 ctcttttaca cgctgtagaa gagcatctaa tgccttctga tattcaggat ctactttagg 43020 ctcgttagtt tctggaacta acagatcctc agatgtggtg acatttgttt gttcggtaat 43080 aacaattgtt ggttgagttt ctgcagaaat aacgtcgcta ggcttttctg cttttgattt 43140 tttgcctcgc tgttttttgg gctcttcacc aaggcgaaca acgctaagat cattattaat 43200 ttcaaaaccg agtgcttttg aaaatgcttt taattgaagc ttggcatttt ctgcatcacg 43260 ttgaacaaat cctcttttaa tagcttcaat gagtgcagca gtttcaaatc ctatgatata 43320 aattgaaggg agatatgtat tgataacaaa aacatcctga cccgctttat actcatcaat 43380 agttaatggc tttgtgaatg taatgccagc cagttcaata gtttcgattt tgatgcagaa 43440 ttcaaaaccc ggtttgccaa aaacagaagc ggggaattga tctaagtcag aaaagtccaa 43500 catgtctcca ataggacgac aaagaacagt tttacctttt tgaagagcta caaatgcttc 43560 agctgcagtg attagattat tcatgctgtc atccccgttt tagctaatgt ttcaatgtct 43620 tgtttaactg ccttaagttt tgctgcttca atttgaataa gggcatcgat acctaagtgc 43680 tcacatactg tttttacgtc taggccacgt tcagcaataa agttttgaag ttcgtctctt 43740 tgttgatctg agataccgtt aaattctggt ggactaatcc aagtgccacg ttgtttatca 43800 aacgtgcaat tcaatgcttt agctctcatt aacattgctt gtcgcatgtt ctggtaatac 43860 atgtgttctt tatcaagcga ctcagttaat tgattaaggt cacctgcatg ctcagcttct 43920 tcacagcttt gtttccagtt ttctagctct tcttgggctt tagctgctgc aagttgtgca 43980 ggcgttaagg tgttaatgtg gtctttagct tgagtaatca ggtcagccaa gaaagtggga 44040 tgtgctttaa gatctggtac ccacacttca ccagtttcac cacctaaagc acctgagttt 44100 ttcgcatgat gtgtaggtga gggtttgaaa ttaataacgc gggcattttt accttcacca 44160 gtagtaacag ttgttagata acccatgaca tctgcgatac ggtaaagctc gttacggttt 44220 ttaccaccta gatctgggcg gtaaataatt tgatcaccgt tttgatcttc tgatgcgtgt 44280 gcaatgaaaa caacatcttt acctaaactg atcaaagtat tgatgtattg cttgaacgtt 44340 tggttcgcta aaccttgagc ctttaacttt aaagagccat ctttttgacg gttatttgcc 44400 gtaagtaaca gatgggtttt aatgcattca agcattgcac ccacggtatc aatgactacg 44460 gttttatatg gtgctaagtc ctgcggagta aggttagcta catcactcca ttgttgtacc 44520 tgtacgactg caccacgacg taattcacca gtacggtgag caccacggtc aaagtcaaaa 44580 gaaattgctt tttccgcagt aaagcccatc gatgatttac ctaaacccgg atccgcgtat 44640 aggtacacaa taattgcttg aaccaataaa gtttggtcag cagtaataat cggtagagcc 44700 attttcttat cctcatctag agccggtgaa gccgcgtttt tgcttatatg ctttgcggtc 44760 ataagtagga atgtttgttt cacgcagttt tattgcgagc tgctttctgc gttgaaagtc 44820 gatttcttgt gtgagttcat tccaaacttt tggatagtcg gtttgaaact tatacacatt 44880 taaaggcgtc ttaaatccgt ctttaacttt gtaaagaact gagccattag cattagatgc 44940 gtacacttgc cagccaatac gaacagagta gaggccctta tcatcacggc ctaaaaatga 45000 cttgtagccg tcggggtgct ttttgaaatg agtcatcttt aagcctcctt acattcgcat 45060 gtaccaacaa aggcatacgt aagcgggcta ggagcatcaa caggtgaaac gtccttaata 45120 tttaaaggaa taatttcttt gcgatattta actaaaacca catcaccttc acggcaattg 45180 acaattcctt ctcttgaaga aaaacgtgca gatttagaag attgggttac tctgcaaaat 45240 gaaacctcat caccagcttt gatttttgaa cggtcaacag gaatcatctt cttgcaagta 45300 gggcagttat aatctttcat taggctgcct ccaaccattt attacggtcg atatagcccg 45360 ctaa 45364 <110> Office of Research Affairs in Yonsei University <120> Lytic Bacteriophage specific for Acinetobacter genus resistant to          carbarpenem <130> IPDB46201 <160> 2 <170> Kopatentin 2.0 <210> 1 <211> 181 <212> PRT <213> Bacteriophage for Acinetobacter genus <400> 1 Met Asn Ile Glu Lys Tyr Leu Asp Glu Leu Ile Lys Arg Glu Gly Gly   1 5 10 15 Tyr Val Asn Asn Pro Ala Asp Arg Gly Gly Ala Thr Lys Tyr Gly Ile              20 25 30 Thr Glu Ala Val Ala Arg Asa Asn Gly Phe Lys Gly Asn Met Arg Asp          35 40 45 Leu Pro Leu Asp Val Ala Lys Ala Ile Tyr Arg Lys Asn Tyr Trp Thr      50 55 60 Ala Pro Arg Phe Asp Gln Val Asn Ile Ser Ser Ala Val Ala Glu  65 70 75 80 Glu Leu Leu Asp Thr Gly Val Asn Cys Gly Thr Gly Phe Ala Lys Pro                  85 90 95 Leu Leu Gln Arg Ala Leu Asn Leu Leu Asn Asn Asn Gly Lys Ala Gly             100 105 110 Trp Pro Asp Leu Ser Val Asp Gly Ile Tyr Gly Pro Ala Thr Leu Asn         115 120 125 Ala Leu Lys Thr Tyr Leu Val Lys Arg Gly Lys Glu Gly Glu Lys Val     130 135 140 Leu Val Arg Val Leu Asn Ile Met Gln Gly Gln Arg Tyr Ile Glu Ile 145 150 155 160 Cys Glu Arg Asn Pro Ser Gln Glu Gln Phe Phe Tyr Gly Trp Ile Ala                 165 170 175 Asn Arg Val Ser Met             180 <210> 2 <211> 45364 <212> DNA <213> Bacteriophage for Acinetobacter genus <400> 2 taaaatattt atgtttttat ggtcgtcatg attggtgaaa tcattccaag gtttgccgct 60 taagtcagtt actgactcaa tagcaaggtt agtaatttca gccgctgtaa aatcagatcc 120 agctacacca tagctatcag ctacaccgtc aaaatcgaag ctcacgttta atttgaagcc 180 gtcaatgcgg ataactgctt caccagattt ttctccagtt ttcttaacag ccagaagttc 240 atattcagaa gcaacgactt gctcgctttc atatgagtaa ttagaaggga cgctagaatt 300 agcagttcga tattcacaag aactcaaggc tacaagtaca gcaattgctg taactccagt 360 taccttatgc ttgtttgaaa aggtttttac gttcataatt gatctcgcag tttgcaaaag 420 cacatcggac ctggggaggg cggtgtgctt ttttgttgtc tgtgagataa atataagaaa 480 acttattttt attgtcaata agaaatctta tttaaattta agaaatctta tttttatgct 540 ttaatagaca aaagaaaacc cacacggggt gggttcgaag gggggattag ttgtaatttt 600 gaggaagttc ccataatgct tctgtcttta gacgcaattt tttttgattt tccttgagac 660 tttctcaat ttcctttatt agtttatgtt gttttactat ttgatcttta acctcttcag 720 gaggattcgg gatctcaata ttcaaaaaca tttcatcagg aatactgcgt cgtctctcta 780 cactgccttg cattttactt ttgtatattt ttcttagaga attagatctc aaaatcaaat 840 ccaaatattc tacattaact tctcgtttta atctaaagat tttgtatgct gggcttacgg 900 cagcagcatc gtaatatttt tgaaatccta gaacaccttc atctataggg aaccccatta 960 caagttcatt tttaaaaacc tttttatacc cagaaatatc agaacttgcg actcgttttt 1020 taaatttctc atgctgatca attaagccat gttccatagt gatactcata ataggtatat 1080 ttgtatcctc tcccactttg actttgccag acaaggatag gagttctttt agttttatag 1140 ttgggaattt tgattttata tgtgaattac tatagtgagc ataattataa atataatcat 1200 tgcttctgat taattctgga ttaactttta agaaacctaa ttcattataa tatttatcaa 1260 agtcgctctt atttaaatca gcaaaatcta aattttttaa atcattttcg tcaatttttc 1320 tacggaaaga atctaaactt aggccatcat ttgtcacatt gtagtaaaaa acgtcagaat 1380 ttgttctacc attatgacag ttggtaaagt agagtatatt ggttttaact tttgcatatg 1440 gcagaaaaac ttcttttgga agtgaaacta ctgcttttag ttgggcgttt tcaaataaat 1500 acttccttac tggagctaaa gcggctttaa aaagaaagcc ttcaggtact actaatgcca 1560 ttcgccctcc tttttttgtt gctttaaagc aatgtagaac acatactcca tcaccatcgt 1620 ttttagctaa cttattctca tataagtgag aataagaagt tttttgagaa aatggcatgt 1680 tggttataac cacatcatat tcagattcaa tagggttttg aagtgtgtct atctggcaaa 1740 ttccactatg cccatcccca tgcagaatca tattcatttt tgcgagtttt gcatttgagg 1800 taatttctct tccaaaaata gtattatgtt taagcttgat ttcttcacta ctattgtttg 1860 caattaaagt gttatctttt atatgatcaa atgcctctgt taaaaaacca cctgtcccac 1920 aaaaagggtc atagatcttt tcaccatatt tagggttgac taagttaaca atggttttag 1980 ttatgtgacg tggagtaaaa tattctccta agtcattatt agttgctgta gcttgctgta 2040 agaaatactc aaaagcatct cctttaatat cggtatctat tgatgagagt tttaacttat 2100 ccaactcttt gatcatctct ttaacagcaa cagggttggt tagctgtaaa tttgtaaaaa 2160 cagaagcacc atattgtcta tcaatatctt gtagtatgtt attagttgta ttaattagca 2220 aatcattatc gagacttttg agagaattcc aaatacctgt attagcattc tctgtataca 2280 attttaaaaa aagaatgttt gcaaattctg aaagcctttc tataccagct cttaaacctt 2340 cacctcttag tgagttattt aacttcttga aaacattaat taactctttg cgagagacta 2400 aaatttcttt aggtgtaata taaataccat ttgtttcctg caatatgaac tctttagctt 2460 catttactct tattaattca ttaacctcat tttcatcaat aaataatggt ttttgggtat 2520 acaaatgccg tgtttcgcag aaaccattat tcattgcaaa tatcaaaggt gcatcaagca 2580 tttcagcata ttcggttgcc tgatccagtg cttttgttaa gctttttcca cctgatttcg 2640 tttcaattac accgattggc cgcttatttt gtgaatcgaa aagaacataa tcgggtcttt 2700 ttttactttt cttgagaaac tcattattaa caattcttaa gatatctgat tcaaaaaaga 2760 catttttgtt tggatcttga atgtccaaga tccagccctt gttaatcaaa ttattgttaa 2820 caataaaacg tgtatcttgc tcaatattag acatattgca taatcccaat atctactata 2880 aaaactattg gcaatctaca cattacacac taaaacatca ataaatatta ctatctaata 2940 agtgatatac cccacattta aaagactgtg tcgggttcac agtttattaa tctttggtgt 3000 tattaatttt ctgacctagc tttccttctt ttaccaactg cacgacctgc tcattagtaa 3060 gcacaggaat aaagactttg tcgccaatat ctttagaaag aatctttact tcttcagcgg 3120 ttagcaccaa agcttcacca tgtttagcag catcattgat gcgagcaata atctgattga 3180 ttggtagttt agagttgtcc ataagtcttc ctgtgattaa tgcgaataag gatgttcttg 3240 tctgtgctga cttggcggca cgatatctgt aatagcggta atactttcaa cctcgtccat 3300 ttcaaagaaa aatcgctcac caccattcac agaaagcaaa cttaaaaccc caccattgat 3360 gccgacaaat tctttaattg tgcatcttcc atccttcaag cacacctgaa caaactcatt 3420 cggcacaagc tctgcatctg gatcgcaaac tacataccaa ccattacgaa ttgctggaaa 3480 cattgagtcg ccagtgcctt taataccata ggctcttggt cctgctgagt gagttggaac 3540 ataaccatca ccaccgttac cttcgtaacc catatctgtg aaatacccat ccatacccat 3600 ctttgaatag gctttaacag gaacgtatct tttttgggtg gggaatggtt taacaggtgt 3660 ttcaataaat ttaacagcat cttcgctatc gggaatattg tattttttct taaaagcttc 3720 gatatccaga actttcaatt gtgcaacagt gctatccaac ttgggaccgc tttcatctcc 3780 attagttata tacgaagtcg acactccgaa ataagcggcc attttgctta atgggtctgc 3840 tttaggagca taagcatctt tctcccaacc agtaacatta ggcgcactaa ccccagcgat 3900 ttttgccaac tcgccttggg ttaatttctt ttctcttcgt aaggcgcgaa tacgctgacc 3960 catagtttct agattcttca tataagttat cttacatctt gcaaaaataa gttatctttg 4020 ttttaatact aagaaatctt attttttgag gttgcacaaa tgaccaaaca ggaagcttat 4080 gagttgcttg gtgtcaatgg tgttggcttg gcaaagttat taggaattga accacctgct 4140 gtttaccagt ggtcaaatga aaaaatccct ttagctcgcg aataccaaat cagagacttg 4200 gcaaatggca aagagccaat caaacgaact acttcaaatg cttaggacct aaccatgagc 4260 aaattatcag ttgatatatc tgcaagcgcc agaaatggcg tatcccgcat attgcatggt 4320 cttgatataa gcaaccaaaa agagattgct gaacaattaa aagttgatcc aagcactatt 4380 actcggctta aaacagataa gaaaaacaat ggcttgaatg aaattgaaat gttttgcgag 4440 ctattgagct tgcttggttt aaaagtcgtt cctaaagatt atcagagcat tgataaagaa 4500 cgggttgctg cacttttagt catgtctaaa agctggatga accgtattga aacagtggat 4560 gacttatttc acgacgaaat cagcgttaag aaagaaaagc ttggatatta aaaaccacta 4620 cctgcgcgaa caggagtggt ttcgcattca caaatttagg aacccatgaa tatgcaaaac 4680 aatttagcaa atcaatcggc taattacaac acaccagaat ttatacctgg tgacgttgta 4740 gtgcttacta aagagtgccg tactttcaaa tcaaatgatt tgtttgaagt taaaaataaa 4800 actttgacta ggttgtggac tatcaaatcg gagaatcatt tgattctggt ttcatcaaaa 4860 gaaatccgta cagcaacagt agcagagctc aacgctaaac gccgcctaac aaaagctgag 4920 caagcattag cggaggtgtc atgaacagct ttacacacca aatcaaagat tctcgccagc 4980 aaagtgaaat ccaatctttc tatgagcctg cattgcgagt acttggccac ctatttgagg 5040 tgaaaaagca aaatttacga aacaaggggt atgacgaaaa taatgcggcg gtaaccaagg 5100 ttgaattttc agaggctatg gctcgtcaat ttcgcataac gcagtggtta gcacaacaga 5160 ttgtaaccag cttaaccaaa gcgtgtttgg ttgattcgtt tggtggctat gttaagccaa 5220 aggatggtga aaagtgagat atgcagcaag aagaaaacag gatatttccg tttccaccac 5280 accgctagag gtggtaattc cactggaaca accagtaaag atctattcgg ctaaagaatt 5340 agcagccatg ccgctttcag ttatgaatgc cgcaattgag gctcaggaaa gattttatca 5400 acttgaagaa ttaacccata tgggggggca ggctatagca gttcgccgtc tcatggagga 5460 tgggcacaaa ctaattcagg tgaaagaaaa gtcgcgcatt cgctacaaaa tcaacaacga 5520 atttattcct ccaagaatta ttcgtcagtt ggaaatgcgc ggattagtga agcttgaaag 5580 gggtaagtaa tgattattat caccacttca aagccccttc gaaccccctt caaaggagat 5640 aaataaccat gcgtgactat gggaaagtct caccacattt ctggacggga actacgggaa 5700 gt; acgcgaacat gcttggcttg tattacatac cccttctata tattgctcat gaaactggct 5820 tgggctttga aggggcttct aaggggcttc aaagagcctg tgaagcgggg ttttgtagct 5880 atgacgaagc cacggagaca gtctgggtgc acgagatggc acgttttcaa gtagctgagt 5940 cattaaagcc agccgataac cgctgtaaga acgtgcaaaa agagtatgat tcattgccgt 6000 caagccctta tttatcaagc tttttcgata aatatgcaca agcattttgt atgactcaaa 6060 agcgtggcga aaacgccaaa atagatagcc ccttacaagc cccttcaaag ccccttcgaa 6120 gccaggaaca ggaacaggag caggagcagg agcaggaaca agaaaatact cacacacaaa 6180 acgcggttga aaatttttca gcggccgagg agtcttggaa accaaatcgt gaactattgc 6240 tgaatgttct taggacttca caagtgggtg cacaagcaga gcaggtttta aaaatgccaa 6300 attatgaatt tcatcttggc aacttcaatg ctcactggga aaacaaaatt gatctcacgg 6360 aaaaccaacg aactcgaaag tttgcaactt ggttaattca ggaattcaca aagtcgataa 6420 gacctaaaaa acaaaactca ccaatgaaaa ctgcaccagc aagagacgta aacagtgctt 6480 ggggtgatgc aaaacagtat gcaccagcca cagatgatat cgatgtaggg gagatgctat 6540 gaatgcattg agcaaacaat tcaaaactga gctggtacaa actaatcagt tttgccctaa 6600 acacaatgag ttaatggttt tactaattgg tcgtccagtt tgccaaacat gtgcaaatga 6660 agcgtatgtg aaatcacaaa ttgaacacgc acaccaagtc aacctcatgg tacgcgagaa 6720 acattttgcc ggagcaaaac tccctgagcg ccacaaggaa agcggattta aaaattatat 6780 ggtgagtatc gatccacaga aagaggctaa agctgcttgc cataaatttg ttcaagattt 6840 taattcaggg aagaagcgca atctgattat ggttgggcgc acaggaacag gaaaaaccca 6900 tcttgcatgt gctattgctc gtaacgtttt agacaagcgg agttatgttc gttacgtcac 6960 ctcagaagac atggcaaatg aaattgccac tgcatggaca aagcctgatg acaatgaagc 7020 aaatgcaatt tttcgcttca cggactgtga tttattgata ttggatgaat atggtttgca 7080 cgaccaacac gagagtcgat tgcagctcgt tcataaagtt ttatatgcac gttatgacga 7140 aaaaaagccg acagttttaa tttccaacat gacgcttgag tctacagaaa aggcgcaagg 7200 tttgaaggaa aacttagggg accgtttatg gtctcggttt caacatgacg gtttgacagt 7260 agttgaatgt gactgggatg acttgcgttt tggtggggca ggatcatgac taaattcgag 7320 attttaagct gtggcttact catttcgtgt gtaacagcag tactttgcgg tgcggtggtt 7380 ttgtggtggt tggcgcgtaa agagcttgat gagaaaggag ccagccatga aagcaactaa 7440 attgattaga gataaaggac tgcaatacgc gaaggaaatc gtagattcag cacccgataa 7500 cgcaactgaa tggaacgagg gttatgagtt ccaatgtggt caaagtgtag aaatcagccc 7560 agcagatcgt gagaagtatt ttgtagattt ggttgagctt aaacgtctgg tggagtcttt 7620 gaaaatcatc aacgatttag gtggagttga gaagctaacg cctgcattca ttacgacaga 7680 taagcatgtt ggttacacgc atgttcgcat ggtgggaaat gggagattga gctttcttga 7740 tgatttttgc gacttcattc cagatggttc catttcaatt aagcgtgtga tgactgctat 7800 ccgcgaccac gaatcaatat acggaggcgg tgaatctcat gccaactaga tataacacag 7860 gcgagtatag ctacgatctt gaatatcact atggagatat gtcagcaagc atggagatgc 7920 ttagagcacg tttaattgaa ttgttgactc ctcatctgtc tggccgttat gtgaaatgga 7980 gagaagcata tttcacaagg tttacaaagt gcggcgggga ttcggggtgg atgttttgtg 8040 taggtccaca cgaatttcat attgatgggg cgttaaggcg ctattactca ggttctattg 8100 atattaccta caaccagaaa gatcgatatt tcttggtggg tgagaaaaga aagtcaaatg 8160 taaggcttgt aaggggtttg gcttcattcg agatgatggg tgggggcata tagataaatg 8220 tgaaatgtgt gatgcagaaa aaggagccag ccatgagtga gtttgagggt aaatctggaa 8280 agtgggcttg ggagattcaa aaagaacaac aagcgaaagt ggaggagctg caaaagcgtt 8340 tagatggggc attaaaagag actcaatatg ctttgcagta tgttgaagaa gacatgcgcg 8400 gcaatcatga atttctacaa atggcaatga ttcgaaccct taaagctata gagcaagtgc 8460 tcaaaggtgg tgcttgatgt catcagtcag cattgctgaa taccgcaagt tatttcccat 8520 aaagaaaata aaaagcgccg ttcagcaaag caagttgcca gacaaccaag tgtgggtgaa 8580 gtggttctgg caacgcattt aagagcatgc aagattggat ttgaacagga atataagttc 8640 catcctgaac gcaaatggag agcagatttt ttaataaagg gttcaaagat tttgattgag 8700 gtagaaggcg ggatctggag cggaggccgt cacacaagag gcaagggcta tttaggggat 8760 atggagaaat acaactccgc agcaatgatg ggttttacag ttttacggtt cagtacagag 8820 caagttaagt ccggtatggc attaaagcaa attgaattat taattaaggg taaataggaa 8880 ggcgattatg ttggttgaaa agtttgattt tattgagtta cttcgccttg ctattgctca 8940 aagcgaaggt aaagggaaaa ttactaagca tgttgttttg ggagaaattg ccttattgcc 9000 tgcaggtgca aaaaaatggg cagaattact gcttgaacgt attgattttg agcgcattgc 9060 agaaatcaca gaaacaaaga aaatttatga gaccaggata attaatggta aggaatcaaa 9120 aaagcgtatt ggtgaaatac cgggtaaagt tgaaataaaa aaaggggaga ttaactcagc 9180 tgattttttc cgcgttagaa acgtactagc gggtaagatc catcgtgaaa tgatcaaaaa 9240 gaactttaag ccaaataatt gtcagggcga tttatcaaat gtggccaaag gtattgctga 9300 ggttgttttg cgtgggcgat tatttacaaa ggcaatgtgt ggccattgcc agggattagg 9360 caaattggag ttatttaatg aaaagggata tccaagcgga tctaagtttt gtgataaatg 9420 cagtggtacg gggaaacgcc catatacatt gcatgaaaaa attacgatcg caaaattaaa 9480 agtgtctaag tctggttatt ctgagcgata tgaaccatat gaattaattg ctgaagcatg 9540 tatcgaaaat tgggaaaaca ccattagaac tagcctggct agatcgtttc attttgaacc 9600 tgaagaaata tcattagctt gacttaaaca gaacggttga gtataagtat ttctaaaatg 9660 ggcgctttat acatggatcg cctgaaaaac ttaataaaag ctcactaatt ttagtgggct 9720 ttttgcgtat ctagagcatt gaaaatggaa aacacctggc atgctgacca agaaaaacca 9780 gaattacggc cagatgaaaa acctttgaat tgcccatttt gtggatctga ttcaatttgt 9840 acggattctt cacattatgg aaaaccagat gaagacggct ctatagcgtg ggatgctttc 9900 acatggtgtc atgattgtgg atcaaaaggc cctagtgctt gggcgatgat cgcttgggat 9960 gaaaattttc attacgacac tgtttatgaa gaaagatcaa ttgttaatta tgctattcgc 10020 cagtggaata cacgcaaata agatttttaa tctcgtgagg ggtgttttat aagcacacct 10080 ctcttttagc cggacggatt acggcgcaaa cggccccgct acatactagt tattggcggg 10140 gctttttctt tttggagtat gtatgactga atttcaaaaa attacgcatg agattagaca 10200 gctccaagta gagttaaatc atttaggaag ctgcaataca aaagacttaa cagcagaaca 10260 gatcgctcac atagatgagc gatttttttt ggccattgaa aagcaaagta aattaattgc 10320 tcgtctcaac aataagccag agggcttctt ataaatattg gtggtgcgat ggatcctaaa 10380 aagtactata tgctcaccag gaaaaaagaa agaaaaccca agccaaagag cacaccatta 10440 ccaaaagcca agcaaaacta tttagaggcc gaagcaactc taaaagaaga attaatcgag 10500 ttggccattg gttttgaaag taagtttcag ccgatccata ccaaacactg gcgctttgat 10560 tttcatatag tgaaattgcg tttgctcatt gaaattgagg gtggtccctg gtctggtggg 10620 cgtggtggaa agctgtcaaa taaagcatgg agtcttaatc gatatgatca tgctgaagag 10680 atgggttaca aaatagagcg ctttcatcca gattctattt tgtcgggata tgtcatcaac 10740 tggataaaaa gtgaattagc gagaattgaa gatggagcag atcagaccat ttcctccaac 10800 tgattttatg gatcaggcag aagaagagga agcaattcgt ttaatacccg ctccagacct 10860 aaagaaatgg gttgtggcca actacttaac gataggtgga cctctttata accctgacca 10920 tgaccatatt gctgagctgc ttcacgataa tgaagaattt ttagcatttg cttgggcctc 10980 ttctgcatat aaaagtaagc aagctatggt gttaggtcag tgcgaaaaag tcatgttcaa 11040 tgttggtgga tggcgtaagg ccagacaaga gcaacagatg cgtgattggt ttggttttgt 11100 acctacttat ttaataactg tcgacgcttc tttctgtgag cgtgcaaacg atacagagtt 11160 ctgttactta cttgaacatg agctttacca cattggagtg atgagagacg aggacggaga 11220 aattgtttat agcgatagtt ctggtcttcc taagcactat cttgctggtc atgacgttga 11280 agagtttatt ggcgtagtta aacgttatgg accaagcaaa aatgttaagc gacttattga 11340 agtcgcaaaa aatccgccgt ttgtttcgaa tcttgatatt tcaaaatgct gcggcaactg 11400 tgtaatcaat tgagcctaat ggctcttttt tttgcccatt ttgttatacg tagttatacg 11460 atgaggaagt tatggcgaca ctaaaagagc ctgtgaaaat ctttatagtt cagtctcttg 11520 cttgtcgtga tacacctcaa gaagtggctg aactcgtaaa acaagagttt ggcgttgata 11580 tagatcgtgt tcaagttgca acttatgacc ctacaaaggt tgctggtaag aacttaagca 11640 aaaagtatgt cgaactattt gaaaaaacca gagatgagtt tgataaaggc ttaattgata 11700 ttccaattgc taataagtac taccgattga agcaatacca aagacaactt gagaagacta 11760 gaaacgtcaa aacagcctta aaaattcttg agcaagccgc taaagacatt ggtggtcaat 11820 ttactaatcg ccaagaaatt acaggcaaag acggcggacc agtccaaaca gttaattcag 11880 aaattccagt tccaatggaa gattacttaa aagcgcggag ggaagtctta gatgagtact 11940 gatgcggctc gggataaagc catccggatc gaggcgcaag aagatttata tttcttcaca 12000 aggtacatgt ttaaggagcg ccgtggttat aaatggatgc aaaattggca ccacttagaa 12060 atctgcgaag ctttaatgaa agtttatcgc ggagagataa agcggttaat tattaacgtt 12120 ccaccacgat attctaaaac tgaaattgct gtaattaatt tcatggcttg gtgttttggt 12180 aagaatccag actgtgagtt tattcatatc agttactcgg caatgcttgc cgcaaataat 12240 gccttccaaa tacgaactct tgtacaagaa gaggcgtata gaaaagtctt tcctgagctt 12300 acattgcgtg atgatagtaa ggctaaagac ttctggagaa cttctcaagg cggtgtctgc 12360 tatgcgacag gtacaggcgg tacgattact ggttttggtg caggaaaact tcgtaaaggc 12420 tttggtggct gcattattat tgatgaccca cataaagcac atgaagcttc atcaaaaact 12480 attcgagaag gggtaattga ttggtttcag aacacactcg aatcgcgtac taactcgcca 12540 gatacgccga tcattgtgat tatgcagcga cttcatgaag atgatttagc tggatggttg 12600 ctaggtgata gaaaagacgg cgttcctgta gctggtggta acggtgaagt gtgggagcat 12660 ctatgtcttt cagctattca ggaagacgga tccgcactgt ggccagcaaa acacaatatc 12720 caaaaattga ggctaatgga gcaagcagca ccatatgtat ttgccgggca gtaccgacaa 12780 atgccatcac cgccagcagg cggttttttt aagcccgaca atattcaaat tgttgatgct 12840 ttgcctgcgg atgtagtgaa acaagttagg gcttgggatt ttggggctac cgaaaatgag 12900 ggcgacttta cagtaggtgt gcgagaagct ctaggcgcag atggttttac ttacattgtc 12960 gatgtaacta gaggacagct tggacctgac aatgtgaata agcgcttaga acaaacagca 13020 aaaatagatg ggaaaaaagt ttctgtgcgt ctaccacaag atcccggtca agctggtaaa 13080 tcacaagcta gttcatttgt gaagcttctt gcgggttata gcgtgatagc taagccaatt 13140 tcaggtgaca agcttacacg tgcacaacca tttgcggccc aagttaacgt aggaaatgta 13200 cgaatgctca aaggtgaatg gaataaggat tttattgatg agcttcgtca ttttcctaat 13260 ggcacacatg acgaccaagt ggatgcagct tcagatgcgt ttaatgaatt acatgaaggt 13320 tttgaagcct tctttgctga tatgggattt gctcgatgag tgatgtaact tttcaacatg 13380 ctgaatatgt taagaacttg ccatactggc aaaaacttga tgatgtttgt gaaggtgaag 13440 atgcagttaa ggctaaaggt gaaaaatatt tgccgatgcc aaatgcacat gataaatcac 13500 ctgcaaataa aagcgcttat gaggcttatc ttacccgtgc agtcttttat gaagtaacag 13560 ggactacatt aaatagttta gttggtgcag cttttgcaac cgatccaagt tttaaatttc 13620 ctccggaact tgctcattta gaacgtaatg caaatggtgc tggtttaagt acttatcaat 13680 tggctcaaaa tggaattcgc catttattga agcattatcg ttgtgcttta tatgtagatt 13740 atcctgatgt gccgccagct cgtaatctag cggaatttaa agcacaaaaa gcctatccga 13800 tgattcattt actaaatgcc cttgatgtag tgaattggga ttcagtaatg atcgataacc 13860 agaaaaagct ttgcttagtg gttatacgtg aatttaagtc tgagcgcggt gctgatggat 13920 ttagtaaaac cgaacaagag caatatcgtg tacttcgttt agagcaagag ggaaatgggg 13980 aatatattta ttccgttcag gtgtacacaa agggtgaaaa gggtaactgg gttggcggag 14040 agaagaagtt tccaacagat tacaacggga atttctggac ctatatacct tttacatttg 14100 taggtgcaat tgataattca gaagagatta aaaagccacc attacttcct ttggctaatc 14160 tcaatttagc ccattacaga gacagtgcgg actttcaaga gtccgttttt tatatggggc 14220 aacctcaata ttatgcgaag ggtgttaatt gggagtggta tgaccaagcc aagaaacgtg 14280 gcatctacat tggagcgaaa gtacttttgc ctttacctga aaatggtggt ttaggaattg 14340 tacaagccga ccctaatact cttgcccggg aagcgatgaa agataagtgg gaaaaaatga 14400 aggagatggg ggcgcgttta attgagaagg gctcgggaag taaaaagacc gctaccgaag 14460 cgaatagtga tgacgccgtt cagcattcag ttctttcgct ctgtgtcgtt aatatgaatg 14520 aagccttgtc agcagcatta cgatgggctg ctaagtttgt aacgcctaat gtggatgttc 14580 taactaaaga tgatttgatg ttcgaaatca gtcaagaatt taacaaacag ggttatttag 14640 ctgagttagc tcgacagtta tttgaagcag ctctacaagg ccgatcttca tttaaatcat 14700 ggtgggaata caaccaaaca ggtatgttcc ctaaacaaaa atatgaagaa gagcttcaga 14760 atgttgaagc agagcaagat gggactttaa atcaaaaggt agagtgagat ggcaacagat 14820 atcaaaaaac tatttgaagt actcactcag caccaggcct atctttatcg tgcttcatca 14880 aaaacggtaa atgagttatt ggctttattc aatgatgata cgagcaagat gctatctaag 14940 cttcgggatt tattggatga gcttaatgag tcggagaaag ttgctttagc tggtggtaaa 15000 tatacaactt caaatttaag ggaaattagg gatttgattg cccaatggtt tgccagtgtt 15060 aatttagcat tacctgaagc ttttgccgtt tctgctacgg cgctggctgt ttatgaggcc 15120 aattacgtag ctaagctcta tggagcaaaa attaataagc ctgatgggga aaaactattc 15180 ttatccgcta aaaaagttcc gttggcaggt ggcgctcttg tcgatgatct gctttcaaga 15240 attgctgaaa gtgcccgtca aaaggttgag tatgcaattc gagatggtat taattcaggc 15300 aaaactaacc aagaaattgt tcagcgtatt cgtggtacca aacggcttaa ctatgaagat 15360 gggatcttaa atggtaccaa aactgatatt gagcgaacgg taagaactgt gcgaagtcat 15420 gtagctaatc aagcctatct aaatagcttc aaccaaattg gctttgaata tgtccgattt 15480 gttagcgttt tagatggacg aacttctaag ctttgcgctt cattagatgg ttcagtgtgg 15540 gaaataaatg atccggcaaa gcgagtgccg ccgttacatc ctaactgtcg cagtatcttg 15600 gttccggtcg agaaggacgg tcaacttgtt ggcgaacggc catttgtaat ggacgaacgt 15660 agagttaaag acatccccaa agaagagcga agccagttaa taggacagtt agatgcaaac 15720 accacattca aagagttctt taagaaaaca gatgatttct ttcaaaggga gtggctaggg 15780 ccaaagcgct ttaagctcta taaagatggg aaatttgatt ttgataagtt ctttgatcct 15840 gaaggccgtt tctatagctt agatgatttg agaaagttgg atgaaaaagc ttttaaaaag 15900 ttgggtctgt aatttttctt atgttatatt ttttaaaaca tcagaattta tacaatatga 15960 aaacaatagc ttttgtatgt ctaaccctaa tttccatcac ttgtttagct gaaccaagtc 16020 aaaaatatct taaagaatat gatcgattgt ctgaagcttt ggagtcagca atggcaaatg 16080 catattcttt tgatcctgca actggtcaag taaaacaggc tactcaaggt ttagaagcta 16140 aaaataattt atgtagagct gcccaggcga aactaaacct caccacgttt ttaaaagaca 16200 atttagagga atctaaagag ctttataaat ctattgatgg tgcagagact ctagataaaa 16260 attatcttag tggacaacag caggaacaac aaaatctcgt ttcaaatttg aaaaaagacc 16320 ttgttggaac tggatttaac tgtgagtaat tattgccgat tacaggtaat tctaaactca 16380 cttaagacac aattttcacc tatataagcg cccaaatggc gcttttgtca tttatggagt 16440 ttggcttatg agtgaatcaa aagttagaca tttggtactt aaaagagttt cagataaatc 16500 ttctcatctt gctctttgtg acgaggaaac aggtattcca ttagctggat taaccgctgt 16560 aaaaatgaat tgtagtgttt ttgagggtcc agcgactatc acggcaacat ttgatgtagg 16620 tggtcctcaa ggcatccgct tagttggtga tgaacctaga caaaaggttt ggagtgcaaa 16680 ggaaacgtag cgaaaggcac tacaaatgcc tgaaaagcaa atcaatatgt cagatgctca 16740 atatattctg agcacaaaat gaattctggt gccatttctt caaattaagg tttcaagcca 16800 tggcaattta tggttttact tttgaaagat taaaagcaat tgcactcatc aaatagaact 16860 taatttttaa ccatagcacc ttcgggtgct ttttttgcga gaagaaaatg ccaagcccta 16920 ttatccaata tttccaatat gaacatttac ctgaacattt gcagcaagtt agtaagccaa 16980 ttggtgattt agctcggcaa atggatgagc aacttcctga cgggcctgaa aaatccacag 17040 gattaagaaa gctacttgaa gcaaaagatg catttgtacg ccaagcttta agtaaataat 17100 catttataga aatgaagcgt cctaaagggc gcttttttat tgcctgccga aagcggatgc 17160 taacggcgaa tccgggcgga tgcccatttt gtatatatag gttggatgac caatgaaact 17220 taaaacagta acaatcgacg gtaaagttta tgcggaagta gacggtgata agccgatcta 17280 tattcatgat gacggcaaag aaatgccaca tgatgcacca cactcggtag caacaattgc 17340 acgcttaaac aatgaagcta aaacacatcg tgaagccaaa gaagcagccg aaaaagcatt 17400 aaaagctttt gaaggaattg aagacccagc ggcagctaaa aaggcattac aaacaatcca 17460 aaatctcgat gataaaaagc tggtggatgc cggtgaagtt gagaaagtta aagctgaagc 17520 tatcaaagca gttgaggaaa aatatgcccc gattgttgcg caacgtgatg ctctagaagc 17580 ctctttacat aaagaactta tcggcggtgg ttttgctcgt tctaagtaca ttcaagacaa 17640 cattgcagta cctgtggaca tggttcaggc aacctttggt catcacttca aaatcgaaga 17700 aggcaaggtg gttgcatatg atccgaacgg cgaaaagatt tattcacgtg tccgcccggg 17760 tgaacttgca aatgttgatg aagctttaga gtcattggtt ggtggatacc agcataaaga 17820 cttaattctt aaaggtggta aaggaactgg tggcggtttt caaggtgggg gcaaaggtgg 17880 agcacctact ggaatgaaac gcagtgaaat gtctgtttct cagaaagcag attacatcaa 17940 agaacatggc aatgatgcct tcctaaaact accgaactaa tcattaaata tttggagata 18000 agtagttatg actacgacag ttaattcaga catgatcatc tacaaccaac tggctcaaac 18060 agcctattta gaacgattac aagacaattt gaatgttttt aatgaagctt ccaatggtgc 18120 gattatttat cgtaatgaaa tcattcaagg tgacttcaat aaaaatgcat tctacaaagt 18180 tggtggtagc attaaacatc gcgatgtgaa ctccaatgca aaagtaactc cggaaaaaat 18240 cggtgcaggt gagtctgtag gtgtaaaaat tccatataaa tatggtcctt atgcatcaac 18300 tgaagaggca tttaagcgcc gtgctcgtac accagaagaa tttgctatgg ttgttggtta 18360 cgatcttgca gatgcattgg ttgcaggccg attagagtac agtttagctt ctttaaaagc 18420 tgctatttct agtaatcccg atatggttgc gaaaggaagt atcgttgttg atggccgcaa 18480 agcattaact cgtggtatgc gaaagtttgg tgataagttt ggccgaattg gcttatgggt 18540 gatgaactca gatacatatt tcgatattgt cgatgatgct atcactaagc aaatttacgg 18600 tgaatctgaa atcgttatct atggtggttt accaggaacc ttaggaaagc cggtattggt 18660 gacggatgct gtaggtgata acgatgcttt tggcttgcag tatggtgctg taacagtaac 18720 tgaatcacaa gtaccgggct tccgagctta tgacatcaat gatgaagaaa acttagcaat 18780 cggtatgcgt gctgaaggtg catttaacct agatattctt ggttatagtt gggatacatc 18840 gaaaggtgaa aatcctgacc ttacattact tggttcaagc gctaactgga ttaaatatgc 18900 aacagcaac aaaatgacag caggtacctt acttgattta tcaggtacag cgacaactgg 18960 ttaaaaccta aaaattaaaa cctaaggggg ctaataagcc ctctttttat tattaagaga 19020 aaagcgccat gaagattatc tatacacgca ttgcagcagc tgctgcatta gagacgggca 19080 ttattgctaa ccctgactat tatgaaaacc caaatttgaa agcaaaagag gtaattattt 19140 acggtaatta tccaaagatt caaaaggatt acgaatcttt agaagttcca gttgaagttc 19200 gtaagttgga agagccacaa aaaacgactt tggccacggt aaatgtcgag gtaggagtca 19260 cccctgaact tcaaactgtg attgatgatg caaaagctga gtgtgaaaag gtagttgaag 19320 aaaacactca gcttaagcag aaaattgcca tcttagagca ggccggcggc aaccagtcag 19380 agttgttatc tgagaattca cgattaaaag atgcagcagt cttagcagat aaagctctca 19440 aagatgctga agctcaagtg gtcggtataa aaactgaatt tgaagctttt aaaaacgata 19500 ttcccgcaat gcaagcacgt attgttgaat tggaagctgg aaaatcggca gaaaacccag 19560 ctacagaaac ggcagctaat gattttgaaa actggtcaaa tgatcaatta aaagagtatt 19620 tggctagtaa aaatattggt tacaagccgt cagcaacaaa agcagaactt cttaaattaa 19680 tccctaagga ataatgcaat gagctttatt actgtagatg acgcaaattc aattttgggc 19740 agcgattttg caccagacaga tgataaagct cgtctggtta aactggcaaa tgtctggatg 19800 aaaaacagaa taggttttgt accagatcct attgacccac ttcttaagga tgcagcttgt 19860 gaaattatca aaggaattct ggccaaggta atttataacg gcaaagatca gcagctgaag 19920 cgcaagaaag ttaaagctga ttctgtagag tcagaaaaag aataccaaga tggatctgaa 19980 gcaatttcta gctttgaaca gatagcaatt gattttattg attcacttga tttgaaagat 20040 ccaaatgcaa gttttaatgg ctttggcata ccactttaca gggcttgata tgggcttacg 20100 tgacgaaatt caggcagaca ttgctgaagc atttaatgat gatttggctg acgccgttca 20160 ttcatttact tgtgagcgga tctcaaaaac taattgggat cctaaaactg aaacatatgt 20220 tgaagttaaa gaaaactatt ccggccgagg cgttctgttt ggctcataca gtcaatatga 20280 gattcagacg cttggagtat tagcaacgga taagaaggcg accttgctgc aaaatgaagt 20340 atccatgaca cctaaaattg atgatgaatg gctaacagct ttaggttcat ttcgagttat 20400 ccatattcaa caagatccag ccagtacaat ctggaaatgt cagcttcgaa aagtgtaggg 20460 gctaaaatgg ttaatcctga ttatgttcct gaatggtata tctcgccttt tcaacatgtg 20520 cagtacacgc ttgctcgaaa tcaactacac atggatttgt tatttgaaga tatggataag 20580 gccgatcaat ttttggatat gggagcggat gcgcaagtta gtactttttc tgatggtgca 20640 tatgcaatcg tccaaattgg tgatacggcg gataaagacc gaattcaagt ttatggattg 20700 cttttacatg aagctgttca tatctggcaa atagtaaaac ggagaatggg tgaacgagag 20760 cctagtgtgg aatttgaagc ttattcaatt caggcaatcg ctcaagaact tttcgaaatg 20820 tacgaagcaa gcgaggtgag caatgggatg gaaggggaaa aagccgtcta gttttagtct 20880 tgatgtgtct aaagcagcag aagaccatgt gaagcatatt gttatggata ctgtgcaatc 20940 tttagttaat ttaagtcccg tcgatactgg tgcataccgt gcttcacata tggtttcggt 21000 tggatctggt gactatggca tacgtggacc tgaaacaaat gctattcagg atgcagctat 21060 tcaagccgtg aagtttaagt tgggcaattt agtttatatc cagaacaacc agccttatgc 21120 agagcgctta gaaaatgggt ggtctgatca agcaccacaa ggaatttaca acaccacctt 21180 tacctttatt tctcagaagt atggcggcta aaatggcaat gactttagag cagacaaggc 21240 aagctattat cgatcgtatg caagctttta ccggtattac gcaagacaga atccagtatc 21300 caaatttacc aggctttaat gtacctaaag atggtgtttg gtgctgctta acgattgcag 21360 gtggtcccag ttttacttct ggcattgcag ataagccatg tactcgccgt accggtaata 21420 tcatgattca atgctttgca cgtcccaatt caggaataat tgaaatcaca aaattgagtg 21480 atgcattact tgcccatttt gaatatttca caatcgaaca cttagaatgt ttgaatggtc 21540 aatccatcta tgcgggtaaa gatgctgatt tcattcagta taatgtgagc attgggtaca 21600 aggtgaattg atatgtcatg tatgctgact ttagaagaaa tcgaaattaa acggcaagag 21660 ctggaaagac atcttgaaga tgttatggct gttgaactga agaagtggca aagcgaaaat 21720 aagctatgtg tttccgatgt gaatatacgc ttggctaatg ttgattgtct cggagggcct 21780 aaacataacg ttgttactgg agtaagtgtt gatttagatt acaaacctta aattacttta 21840 attaaatgac cgctaagaag cagtttttta cgtctttcta ctaccacctc atcggtggtt 21900 tttttatgtc tataggaatc acttatgagc aattttgttt ttaagcgtgg tgacacattc 21960 aacttgaact tgcagctggt tgatatggat gaaaccctgc agtatccacc ggatgatgtt 22020 cgccgtgcaa ttgatctaac cggttacacc tttacttcac agattaaagc tttggctgat 22080 ggagcagctg tagctacctt gacttgtgct gcattaaatc aaagtacaca gaagggatgg 22140 ctgaatatta aatctagtgc aagcactgca acttggcctt tagggctgtg tcagatggat 22200 attaaagctg tagttagtgg tactacgcag cacactgaaa ctttgacttt ccaagtgatt 22260 gacggggtaa cagcataatg gcaaatcttg tttttaaatt tagttgggat caccggccat 22320 tcccgtataa ctcggctcag ggaaaacggc aattcatgct gccattcgct tcaggcattc 22380 ctaatctggc accaaacttt tcgcaggtcc aaggtactgc tgcagtctct caaggtggta 22440 ctggggcaac cactgcagca gaagcgcgaa ataatcttgg tgctgctgaa aaaggtgtaa 22500 atactgacat tactgaaatg aaaggtttag ctactccact ttcagttgcg caaggtggaa 22560 cgggtgcttc ttctacagca ggtgctcgtt tagttcttgg tttaggtgat atagggactt 22620 ctggattttt tggaagtaaa attagcgagc tatataacaa ggtgtcggtt ccacaatgga 22680 tagctgtatt aggtgataac aagttcactt tcctatcaag tggcgactgg caagcgggga 22740 atacaaagaa cccacttaat atgcctagcc gatatggttc tttaatgtcg tatttgggat 22800 caagctcata tggaacgtat tcatggcaga tttttaaggc agtattgggt ggacagcttt 22860 cctaccgata tggggcagga aataatgtct ggactacatg gggacacatt aaaaccagct 22920 ttaatacatc agtcgatgca aatgggttct taaaatcggc atcaccagta gtgaagttat 22980 ttaatgatca tattgaactt aatagtgatg cagaaaagca accaatcgaa tttaagaaag 23040 ttgatgtagg cgattattta cttaaaggct ctttaggctt tgctcaagaa ggttggtata 23100 tcgaagcacc taaagacgca aacggcaaca caatcgttgc agtagtgtat gacaccctag 23160 aaaatggtga catctcaatt aaaacttaca agcgtaagtt tgattttgaa cttgctgctg 23220 ttgtggcaga tcacgagaac ccaatggaca ttccagaagg ccgctggatt gatatccgtc 23280 tgcatgaaga acctgaacca gaacctgagg ttgaagaaac tttgagtgaa acaccagtgg 23340 atttccagcc gactaactta tctcaggcag ttgctgcagc catgaatggc gtggaaccgc 23400 cagaaatctc agacacagac gaaacacttt aataacccgc ttaaaaagcg ggttttttat 23460 tgcctaaatt ttggagaacc ataaatgagt tcaggcgcaa aaattcgatt atatgcttgt 23520 gaagaagcag ttttaggaac aactcctgca aatccagtct ggtacaccgt tcgccgtgtt 23580 actgatagtt tgactgaaaa tgttactact gaagatagca gtgaagtagt tgattcacgt 23640 tttcgccaag gcgctgttgt aacggaagcc gaagtaactg gtcaactaga gtttgaatta 23700 tcactaggta cctttgactt attcttaaat gttctcgctt tcaataactg ggctgcaaat 23760 gctttaagtt ttggtggtgg agtacgtaag tctcttacct tggtaaaagt ctttgaagat 23820 attggtcaag tctttattta tcgtggtatt caagtgaata caggtgaaat gacgatccag 23880 accacaggca aaatcactgg taactttggt ttagtaggta gctcatttac gcgacagcag 23940 gttaatcctg ttacaaatcc tattccagca tcgactcgcc ctctggtgag tatgccaaat 24000 gttgaaaagc tacttattaa tggtcaatca attcagggta aagcttgtct gcagacactt 24060 accatcaact ttagtaataa tctggaagcg atccgttgta tcggttctgg taagtacacg 24120 cctgagtttt acttagagaa aatgatggat attggcgtaa atgctaattt catgttttca 24180 gcaacatctg cttcttggat tgatgctatt aaaacccgtg atgtatttac attgaccttc 24240 gatattacag ataccaaagg cagtaagtac tcgtttaact tcccgcaact tgaagttaag 24300 gaagcaaatc accctgatgg tggtggcgat gacattatta caatagatat caattttgcc 24360 caagtgcgta ccagtccaac gattgtacgt gctcttgtgt aatcaactta ttcagtaaca 24420 aagcctatgg aaacccatgg gcttttttat ttctaaaaat tagaggttgt tatggcttta 24480 aaagtcggaa ttattaaaag ctcggacgta tcaaaatggt gtgaatacaa gggggttgat 24540 ggcgaagtac aggcagagtt caaagtccgt ggtatcgcct ataaaccttt tcaggtagca 24600 attgaacgag ccggaaatca gatttcatcc aaaggctatg atgtgatggt caaagatgaa 24660 aatgccaagc tttaccatga attgttaatg gatgcgtgtg ctgcccactt aattgaagac 24720 tggaaaggtg tggtatttgc cgaaatcgta gacggtaaaa cggttgaatc tgaaaagcca 24780 tatacacctg agaatgcctc aaagcttctt aatcttggtg atattggtat ttcaatctgg 24840 ctattcatta aagaacaggc tcagaggatt caggaagaag ccgacaagga taaggcttta 24900 attctgggaa agtcgtcgag ctctacaaat accaaaaaac gtatgcgtcg aaaacgccgc 24960 acgaaatcga gcaaatcaag ttcttaggtg gccgtattcc ggatccgcca gaatattcgt 25020 atgcggccga ctctattctt tcggcattta gtactattgc cagatccaga cggtatgagc 25080 agggtatccc gttatcttta gatcagcagg caatcaatgt ctatgcagag cataatgatt 25140 tacccgtggc tgctcatatt tttaatgact gtatttttgc tttggataac ctgtttctgg 25200 atgagtgcca taagaagttt aaggcaaaaa aataaaatgt tttaaagctt tattccttaa 25260 agcttaatca agtgcgggat attttaagaa ataaactata taccgcactt ttagcatagt 25320 atttctaaaa tccttaatag caagtttgtt aagttgttga attttaatat tttaaatttc 25380 aaggctaggt gtttaagaat gtaatttcta gttgacataa atgtcattaa gaaatattat 25440 attttcaata gtaaattata tcgtacgaaa tattgttgaa tcgcacgatt actattaatg 25500 ttaattttat ttaactgatt atcttattct attttggaaa ttattatgaa agctccagca 25560 atgttggtaa caccaacttt tggtgttgat tcatctcaaa aaattcttca agaagctcag 25620 aaaaaaatta cgccagctcg taaatcacgc cttgagcagc ttgctcaaat agcaaaaaac 25680 gcatttaaaa attaattatg aggtttcaat ttgtccacag agattaatat ttctgaggtc 25740 gagttacgaa atttagattc agtagaaaag catctttatc aagatttttg ttgtgagcgt 25800 gaagagctca atacgttctt gattgaagat gcttttgatt atcataatta tggtttaacc 25860 cgaactactt tggtatttca taacgatgta ctgattggct attttagctt gtcagctgat 25920 aaaattgtgc tcactcaaac agaaattgat gaattatctt taaatgggga atttaaagta 25980 acttatttcc ctgcagtaaa gattacaaaa cttgctattc agaaagcttt tgctggcaag 26040 gggtatggta ggcttatttt ggaattaatt gaaggcctag tgtatggtca acatatggct 26100 ataagatttt tgactttaga tgctgtaaat gaggaaaaag ttcttaagtt ttatgagcga 26160 aatggattta atgaaagtct ccatgaagct agacagcaaa gacaaaagca aaataggcaa 26220 acgatattaa tgcataaaga tatctttagt gaataaacca ccttcgggtg gttttccttt 26280 atgtgacatt taatgatcag tttgctaaat tacccccaaa tatgagggta tttttatgct 26340 taaggactat cttgggcctg ccgctgaaca taagcacaaa gcagaacaag ccattaaaga 26400 aaagagattt gatgatgctt ggcgtcatct taatgagcaa aaaataaatt attttcagca 26460 cgcaaaacaa tgtaatttta ctgaaaagca aactttgggg cttgatgcgg ttgtgcacat 26520 cacaatgggc aatttactga gaagagaagg taagcattta caagctttgt atcacattgc 26580 ttatgtttat aaggtaggta agctagagaa cccccaaaat gacagtaacg atgataggct 26640 aagaatctac tataaaagag caaagaaaga tggtggattc gagaacttta aacaagggct 26700 tgaccttttt cccagttatg attatcagtc agtgcaacat ttcacaagca gccttttaaa 26760 ttctggagac gtaaaacaag gagctattac ttctcctcaa attgaggaaa agcctattac 26820 aaaaatccca gaaattaata agaacgctat aaataataag tttttggctg aacgcaagaa 26880 aaaaaaggaa gaacatattg ggattcctcc tccattaaaa aagcccgaga agaagcaagt 26940 tattcaatat gaaaagacga atagccaaat aagtgcaaca cctgttagca gtagttcaaa 27000 aactgaagga tgtaggagtt cggtttcagg gttctttatt gcagcgactt gcgtggtgat 27060 aggtttaatt ctgcttgttt ggttgctttc atactaaaat agtaaactag agaataaaca 27120 cgctacatgt taaattttac tcaaagataa tggtttggga atatgaaaaa gattatttta 27180 ttaggtttaa tattaggttt agcagggtgt atgtctactg ctaatttttt tgaagtgcaa 27240 gccacctctg ttcagaatag cggttattgg accgggcaat atgatcgatt agtaggaaca 27300 ttaaagttaa attccgatgg aactggtgtt atttgtcagg atggaatggg aacagcgaga 27360 gtaatgtctg ttaaaaaatc aaatgataaa ctctattcac aggatggcag cttctggaaa 27420 gtgcaaaatg aaacactcaa ctctatgaaa ttaaattatg caattggtgg tggttatgaa 27480 atgaaaaaag atgatgattt atctttggca acaccagcat gtaaagaaaa attgaaatga 27540 attcaaaatg atttgttaaa aatttgactt agatcaggtt ttttattttt gattaatgac 27600 cgccttttgg cggtttttta ttgcctagag gaaagtaaag atggcacaag aatcccgttt 27660 ggtcattgtt attgattcgc aaaatgctga acgtaatgcg cgtaatctag gcaatgagct 27720 caatagcatt gagcgtaaag gtgaatttgc atctaagtct atggacagct tgtctgtagc 27780 caccagagct ttagctggac acatggctgg tttattaaca gtaggttcag ccatttcaaa 27840 gatggataca tatactggat tacaaaatcg ccttaagtta gtcactaaca atcaagttga 27900 actaaataaa gcaacggaag acactttccg aattcctcaa aaaacctatt cagcatggga 27960 ttctgttcta caggtctacc agcgttttag tgataatgcc aaaactttaa acctcacaat 28020 ggatgacact gctcgactaa ctgaaacagt atcaaaagca gttgcgatca gtggtgcaag 28080 cgcagaagct gctgatgcag ctttagtaca atttgggcag gctttggcaa gcggtacatt 28140 acgtggtgaa gaactcaact cagttatgga acaaacacca gctctagcaa aggctattgc 28200 tcaaggcatg gggatcaccg taggagagtt gcgttcagtt gcggctgaag gaaaaattac 28260 ttcacaagaa atcgttaaag cgcttaaaaa tgtccaagat gaagttgatg ctctttttgc 28320 taaaactgac attacaattg gtcaatcatt aactctactt aataatgaaa ttactaaatt 28380 tgtaggagag gctggtaaag gaagcggagc agcacaggct ttatcaggat cgattcagtt 28440 attagcaaat aatttgaatt taattgcaga cagtgcattt gccataggta ttggcttaat 28500 gacaaaagcc gttttaacaa aaacggttgc tgtacaagcg agcattgctg cgtcaaccaa 28560 acaagtgttt gccacaattg ctgaacgtaa tgcaaatatt gcagcagcaa aagctgaagt 28620 ggaatctgcg cttgccgaag cacaaagtac acaggtgaca ctaacgaaca tcaaagctac 28680 tcatgctcag atcatggcag aaatagaact cgaaaaagtt cgtttaaaag cccaaatcac 28740 tgaacaaggt cgcacggcta ccatcacacg aatggctcag cttggacgat tacaagctca 28800 agttgcgtta gaggttgctg ctgcggaaac agcacagtct gcagcttcat ctagattatc 28860 agcagcctta acagcgcaat ctgttgctac tagccgttta gctttagcaa agtcagcgct 28920 tatggcgatt tttagcccaa tgggtttagc aattgcagca acagccgcat ctttctattt 28980 actaagcagc agttcggatg aagtcaaaga gtctcttgca acacaatctg actcggttag 29040 tgatttaaca gataagtaca taaagttaaa tactgtgcaa gcattaacag agggtgtgcg 29100 gttacgcaaa gagattgagc agcaaaatga tgcaattgat gatgctagtg gagctatcaa 29160 acgttttgct tatatccaaa aggaattatt taaattatct ggcagtgatt atgaagatta 29220 tcaaaatgcc attaagtcta ttgctacagg tgcaagcgat gcaggtgatc tcttaaaaaa 29280 gatgatttca tctggtcgtt ttagtcagac tcaaattgat aaacttattg agttctctag 29340 tgtagtagca gaatcaaaaa ataagattga gcagggtaat actgctctaa aactcttaaa 29400 tgctacttct ggacaacatg ttgaggtaac ggccgaatca attaagcaat taactattca 29460 aaccaactta acaaaagttg ctactcaaaa tttcactgac atgaaaacac aaatgcttga 29520 ttcattacga gcacaagtgg aattcattcg gttaaatggt ggtagcgaag aacaagttaa 29580 atcgttgaat aaggtaatcc aggcatattc tttaaatcaa atttcagcaa ctgatgctgt 29640 ggacaagttc aacagtactg ccaaagttcc tgctgaaaat atcaaggggt tacaggatta 29700 tgctactaaa acggatcagt ctaaaattgc gttgaatcag gctaatgctg agctgaagaa 29760 acaaaacgac ttacgtaatg agtacctaaa acaacatcaa actgtacttg gtgctcaaca 29820 aggagaaaca aatgaattaa ataaccaagt cgctgcacaa gaaaagttaa ataagttacg 29880 agacaacgcc aacaaagata ttctgaaaaa tgattttctt ataaaaaaca ctaaggcatt 29940 tggtggtggc gaaaagggtc ttgataaggc gcgtgcggca tcagagtttt ataccgacaa 30000 taaaattccg atgactagaa gtttaactag tcaggaagct gcaatttttg aggcttggta 30060 taagaagcag aaggaagcca aggacttaca agaaagtatt accgaatcta gcagaaagca 30120 aacaaaagag gttgaaaaac aaaccaaaga gtctgccaaa caagctgttc tacttgctgg 30180 aaatgatgag cgagtgagaa atatgctacg agtgtatctg gcatttcgaa atgcaggttt 30240 aggcgataaa caagctcgtg taatgacagc tcaagttgga cgagagactg attttagaaa 30300 tgaggcaatg tttggtagcc ataaggatga aaataatggt tatacaaata ctggattttt 30360 atcatggcaa aaaagtcgct caactaaatt aatgcagtct ttacaagggc aaggagtctt 30420 ggataaaaac ggtaaaatcc agcaaactca agatgcatta gatgcaatgg ctaaacacgc 30480 tgtgcaagag gcgatgaccg ataaaagtta tagtaaatct aaagcagctc ttcttaatga 30540 cgatttagac tatcgaagtt tagagagaat tgttgccaaa aattttgttg gctgggacta 30600 tgacgggaaa aagcttggca aagctaaagc ttcacagcat ttagccaaac aagactctta 30660 ctataatcag cttagtaaaa ttttagggga taaccccgaa gcagcctcaa aagcaattag 30720 tgatctttcg aaattcgaag atgaagcata taaggcacgt gcaaaaactc ttgaggaaat 30780 taagcagctc caagcaacat atgattcaga aacagttgct agaagcaaaa aacgtgagga 30840 ggaaatcaac aaagcaacca ttttaggtca atcaaattta atcccaaaaa ttaatgagcg 30900 ttatgatgct gaagataagt tagctcagaa gcaatttgat tttgaagtaa atggttataa 30960 gtggactgag aagcaaaagc ttgagtacac atatgaaatc aattctttgc gattagttgc 31020 tgaaggcaaa ctctctgaag atcaaagaaa ggttgcttta gatggcctgg aattgcaaaa 31080 gcagcaagag ttaggattac taaaacttgc tcaggaacag cggttgtttc aggctgagca 31140 attcatgctg ggagaaatgg agcgtatcaa aaaacgttat gcgcttgagt atgatgaaat 31200 atcaaaaatc actgatcttg aagagcgtag aaggaagatg agtgcatttc aggctgattt 31260 tattcgtaat ggtgtgggga atccaacaat tgatcagtat gatacctcta gtcagtttct 31320 taaatcgaca aactacacca agcccaagca aaccaatatg caagtattgg atgaagatta 31380 cgctcaaact tatcaaaagt tgaaagataa tcttgcagct gttttggagt ctgaaaaagc 31440 tagttatcag gaacgattgg aggcggagcg cgtattcaaa gaagcaagac agcaaatgga 31500 taatgagtac cacctgaagg cgattgatgc aagaaaagca gatcacgaca gtcaattgca 31560 attatacagt cagatgattt catctgcttc aagcacatgg ggaggtttaa ctcaaattgt 31620 taaggatgcg cgtggtgaaa attcacgctc tttcaaggca atgtttatag ctcaacaatc 31680 ctttgctatt gcttctgcga ttatctctgc tcatttggca gctacacaag tagctgctga 31740 tgcaacgatc ccattttttg gggcaaaaat tgcggcttca accgccatgc ttgctatggg 31800 atatgcaaat gctggtttga ttgctgggca aacaatagct ggattctcag atggtggtta 31860 cactggatct ggtagaaaat atgaacctgc aggtattgtc cataaaggag aggtggtatg 31920 gtcccaagag gatattaaac gctggggcgg agttggttta gttgagaaaa tgcgtaagag 31980 tgcaaaccct gaagcttttc tcaataacaa tgcctcggca gatagtgtca tgcgccgtgc 32040 aatgatgagt tctaatgcct ttatagaaag ccaaaagcag gctgacatct ttaatcaacc 32100 agttcaagat actcagatta tctataaggg taatagagac acacctaagt tagcttcttc 32160 ggcaaattct gacctgttcc atgatggcaa ggtctacttc tcatccaatg gtatagttca 32220 ggatcgctca aatctggatg atgttcagga ctttacttta ggacgtactt cacgccctca 32280 agctgagatt atgccttcaa ttgagcaatc ctctccaact atcaatttca agattgaagt 32340 cgtgaatcaa gtcagtggtg caactgttga agctgaacaa ttggatgaga aaactgtccg 32400 gatcattgtt acagatgaac tggataagca gcttccaaga aaggtaccta agcttgtaag 32460 tgatcaaatc gcaaatccaa actcaaccat tagtcggtct ttgactgaga atacgacagc 32520 aagacggaat cgataatgaa caaaaccgcc ttcgggggcg gttttttcaa actttttaag 32580 attcaaaaat cttcgtaata cttagaatga ttctgagaga aatgattaat ttcatgtatc 32640 ttataaaata aattcagtaa gattgtagat atatctttta tctttattaa gacatgaaaa 32700 caccaattcc aaaaaccaaa atggatgagt taggttcgct gataaacggc ttcaagcctt 32760 ttgaagtcct tagtgagttt aattatgtaa ggtgtatgcg gttacttgat agtagtaaac 32820 agactgcacc taaggatctt tggcatgtta tgaaagggct tatagagtta aatgctaata 32880 atttaagtga agcaaatgag gcagcattat atgttttaaa acattccaat aattttagtt 32940 gtttaaggaa tgcaatttat atttttaatc atacttttga ttttgataat gtatgtaaaa 33000 caacagataa aattgtaaag ctaattgaat tacaaaaaat ggattccaaa ggaatcttac 33060 caagagatct tggacttatt ttcttactta atggtgagtt atgggctaag gactcatcat 33120 tttatagtga agctgtgttt aataacagtt ttgatcatca cactgtactg gctgatatca 33180 atgatcgact agatataagt gaaaatgatt tcaaaaagat ctcttctatt atcaagaata 33240 ccgttttaaa gaataatgcg agagtactca accatgacta tagctttatt gatgaagaat 33300 ttttattact tatatatata aataaacctg taaaagagat catgaaaatt aacgaggaaa 33360 ttattgaatt atgttttaaa gaaggtcttt tgactgcatt taacaagatc tcatatacat 33420 tcgttcctta tagtgaggtt ctgaatggat aataagcttt tagaatattg taatgaaata 33480 gcatctgctg aaacctcata cccagattta caattaagaa atgttatcgg tagagcttat 33540 tacttcacat ttcatgaagc aaaatatcat cttgaagata gattgaggtg gaagccaact 33600 tcagaaaaag gtggggttca tgcaaggtta tatagcagtc ttctcagtta tgattcaaat 33660 gctaatgaac aaactaaaat aaatgcagag ctagtttatg caaagatcaa ttctttaaaa 33720 aaattaagaa ctagggctga ctataaaatg gaaataaaga ttacgcgcga acttgcaaat 33780 tttagtattg aagaagctaa aagaatttct gagttatttg aactaattta atttacaaca 33840 tttgaaaaaa ccgaccttaa atggtcggtt ttttattacc tgaaggaaag ttatgtacaa 33900 gttaaagcta aatcctcaga ccagcggcta tggcgtaaca ccgggtgatg atgtgaaacg 33960 tcagcagatg gatggcggac gtggtcgcta ttacatcgat gtaaaacgta atagtcatat 34020 tgtcgatgtg aactggaatt taagtaaaac cgatttcaat aaaatgatgg ctttctggcg 34080 gatctatcag aataagccag cttcattcta tgcggatttg gtcatagacc aaggaacacg 34140 tcagcaatac caatgcaatt tcattccgaa ctcgttcaag accaatgaag tgaatggcaa 34200 cctttaccgg gtaaatgcac agctcgaagt tgttcaaaac cagcctaacc ttacggccga 34260 tatagctttg attaaggatt gggaggtcta atggataacg aatacgccaa gttctttttc 34320 aatcgtaaag tcgatgttta tcaactggaa tgtattgagc tttctcatcc ttcctttatg 34380 aacatatacc gaatagttcg taatgatgat cgtggggtgt atgtacaaca taaggaagga 34440 tccggtcagg tctattatga atttttgcca gcatctattc aaagatccgg aatgctgggt 34500 gatctggacc agacattaac cgtttctatc tctggtctag gtgatgtgat gccagatgag 34560 tttgaacggg taatcgaagg gcaatatcca gatgtaaagc caaccgtaaa ttaccggatt 34620 tacagttcag acaatctgaa ctctccaatg ttttatttac ttggactgca actctccagt 34680 gttgccatga accataaagc tgtgacgttc aaagctgaat ctccacgatt aaataccgct 34740 aaaactggag atatctttgc actagaccgc tttactggtc tcaagggggc tatatgaaaa 34800 gtcatgatca tttgcttgat agacaatatg acgaggaaaa ctacaactgt gttcattttg 34860 ctcatgaagc tgcattggat ctatatggaa tagaccgggt ggaagcactt gaatttttta 34920 tgaagcctat taaagaaaag gtatttctac catcaaggtt aaaactttta aatccactgc 34980 ccatgcccaa ggaaggctgc atagtcgcct ttcactcgag ataccgaaac aagcccccac 35040 atgtggggct ttttcgtttg gggcgtattt tgcatttgca ggaatcaggc gtttcatgga 35100 tgccaattca agtcgttcaa gcatttggat ttaatcgtgt gagtttctat gattaagatt 35160 atttataaac aagacccttt atccgaagac aaaacaattg aacacgccga aactttgggt 35220 caatggctta cttcaaaata tgattatatg cctgaacatg tccgtatttt ccatacaaca 35280 agtaatatgg atcatgccga aatttcattt gcgaatgaag tcacaccgaa gaatgcatat 35340 gaattaaagc agctcgattt cttgccaggc actttcattg taattgagaa tcccaagggt 35400 atagacccca taactctagc ttggatagcg gttgcttcta tagttatggg tgtggctgtt 35460 gcattattaa tgcctgtgcc ctcaattacc caaaccaacc agaataacaa tcaatcctcg 35520 tctgcaaata acgaattatc aaaccgtgaa aataaaactc gcgtaaatgg tcgtatcgca 35580 gatatttatg gtgccgctca cgatacccct gatctgatta ctgtgcctta caaggtatat 35640 gaaaacaatg tcgaagtaga gcatgttgtt ggttgtattg gtcgtggtca ctataaaatt 35700 aacggtgcat atgatggtga aaccaacatt gttgatattg ccggcgcatc ggtagaagtc 35760 tttcgaccag gtgtagatat tgtttcaggt gagccatatt tttcgcttgg taccgaaatt 35820 accacgccgc cactaacggt tcagcatcaa acttctgtta atggccaagt tctccgtcca 35880 gcagatacac agtctttaga aggtacgaac taccttcatt ttgcatatcc aaacgagatc 35940 cttcgggcat ctgcaaacaa tacggattta accactaagt ttgtaagtaa tgaccgcgta 36000 gaaatcacca atgcctcatt cacgtttaac ggccagactt atgatttaaa cggcacttac 36060 agcgttctat cggtagcaga tgatcgaatg acgttatcaa atccggcggc cgttaatgct 36120 aactggttaa agcttaaaga gttaaataac caacaaactg cagctttgtc accaaagatc 36180 agttcaatag gtgaaaaatg gattggtcca ttcattctgg acaatgttga acgtagccgg 36240 gtgctgtgta attttgtggc cacaaatgga ctttataccg tttcttcagg tgggaatcag 36300 gccgctgtta acgtcacgat tgaagttgaa gtaacaccgg taaatgaatc tggtgcagcg 36360 attggtaatc cgatgctgaa gcagatcatt ttgaaaggtt cggcaaagtc gcgtcaaacc 36420 gttggcgcaa cgctggatat ggtgacattt caaggtcgct gtagtgtccg tgcacgtcgt 36480 ttaacaccaa caccggcggt tacaacggta gtagatgaag taaagtggca ggcgctttat 36540 ggtgcttatc ctttgcaaag cacagtgtat gaacatgaaa cggtttttcg tgcgcgcact 36600 tatgcaacca ctggagcttt atctgttaag tcccgcaaga tcaattttga tcttcagcgg 36660 atgttaccga cttttaaaaa cggcgcaatg acgacagagc tatttccaac atcaagcttt 36720 gctgatgcat tggtttcaat ggcactggat gacaagatag gccgccgtac gatcgacgaa 36780 atagatctgg aaaatatcta tcggacttat aacgatgtag ttgattattt tggtacacca 36840 cttgcggctg agttctgtac tacgattgat gatacaaacc tgtcttttga agagctggtc 36900 accaatcttt gtgatgccgt gttttgtact gcatatcgtc aaaataataa gctcaagctt 36960 tattttgaac gtccaactga taactcggta atgctattta acttcaggaa tattattcct 37020 gatagttaca agcatgatct tacctttggc gtgatggatg actacgatgg actgatctat 37080 gaatacacgg atccggccga cgatagtcgt atcaatatct atctaccgga taaaggggcc 37140 aagaacccca aagaggtgaa atctgtaggt gtgcgtaaca agtggcaagc tcattttaat 37200 gcgtaccggc tttggaacaa gcttcgcttc cagcgcaaat ccattacctt tgatgcggca 37260 cctgagtcag aattactggt tttacgtgac cggatcgctg tagctgatta tcgcaatggt 37320 attcatcaaa gcggtgaggt ggtacagcaa gaaggtttaa ttctcaccct aagccatgat 37380 gtcgatttca ttgcaggcaa gagttatgtg atttatttgc aaatggggga tggtaccgtg 37440 gacctgattc ccgttacgcc gggttcagcc aagaacaaag tagttttagg gcgtttaccg 37500 aacggggcct taaagcttag tcccgatgac tttgtgaata ctatctacac cgtagttaat 37560 gacgatacca aaggctcact gccttatctg gttgcaaaaa gagaaccggc tgaccagttc 37620 tctaatacca ttactgcaat taattacgat gaacgttatt acctcaatga caaggacttt 37680 attgatgtgc cggttgatga ttcaccgatt tacattcgat atgaccagct ggatattaat 37740 ctggcacgtt tatatcagat gcaaagaggg gatttgccaa cgactggaga aatcagtttt 37800 gtagttgaag caggtgcact agtttcaagt tcaagttctt atcgaccgga aaccagattt 37860 gtctataaat tcgactataa ctctagtcct gcaaaacgag agtatatcgt tccagctgca 37920 tcagaattac ctgctattga tactggtgag ttcccacctg atctcgtggt aaatttgact 37980 attaaaggtg ctgttgttgg acgtggtgga gatggcgggt tgccacattt ggcatttggt 38040 gcatggtcta ccgatccgga ttataacttt actaaaaccc gccgtgacgg ttttcaggga 38100 gcacccggtt tattaaaccg gcacagtaaa ctaaacctga ttattgatgg tggaactctg 38160 gctcgaggcg gctcaggtgg tggagcaaca ccaagcggta tttatacagg attatcgtat 38220 ggagttcagg gtattcccgg tggagctgga gcaccttttg gtcgggttat gaccggacaa 38280 cctattacta acgattcaca agactggcgt tggtacttaa atggtgactt tatggttgtc 38340 aaagtaaccg atgccgaagc ttcggtaccc ggtaaaggtt accgaaccca aaatgatcga 38400 tatggatctc cattgtctgg tgatggtgga ggttggggcc agcgcggtac caagtccacc 38460 aatgatggaa catggaactg gcaataccat ggcacaactg aaggccagcc ggggccgggt 38520 ggacctgcaa ttgttggggt ggcaccactt acaactcaat tgatcaatgg agggaaaatt 38580 ctacaaacac tttaaatctt aaaagaactt tgagcaccca attcgggtgc ttttttattg 38640 cctaaatttt ctggagatat aaatggaacc agtttccaca agcggtttaa cagcaatttt 38700 aaaattttat ggagcggcaa tcatggtgac tttagcggtc gctttagttg cagcagtagt 38760 attaatgaca cgtatgccac gctcaccaca agagtgggca gtgggcttga tctgtacggt 38820 tgtatcaagt ttggctggcg gctcattcat tattgtgaag tgggggcttc atgaatgggt 38880 tactgatgta tgggggatga ttgctctagg tgggttcttc tttgtttgtg gattacccgg 38940 ttgggctttg gtccgttgga tttttaactt catagataaa caggaaggta aaacgattgt 39000 ggaagtgatc aaagagttta agaaagccag aaaagacatt gaaaacagtt aatgccgcct 39060 tcgggcggtt ttttattgcc taaaggaaac cgaaatgaac attgaaaaat atcttgatga 39120 attaattaag cgcgaaggtg gttacgtaaa taacccagca gaccgtggtg gtgcaactaa 39180 gtatggaatt actgaagcag ttgctcgagc aaatggattc aaaggtaata tgcgagattt 39240 acctctggat gtggccaaag caatttatcg caaaaactat tggacagccc cacgttttga 39300 tcaggtgaat atcatttctt ctgctgtagc tgaagagctt ctagacactg gtgtgaattg 39360 cggtaccgga tttgcaaaac ctcttttaca acgtgctttg aatctcctaa ataacaatgg 39420 taaagcaggg tggccagatt tatcagtaga tgggatatat ggtccggcaa ctcttaatgc 39480 actcaaaact tatttggtca aacgcgggaa agaaggagaa aaagttttag ttcgagttct 39540 gaatattatg caaggtcagc gttacattga aatctgtgag cgcaatccaa gccaagaaca 39600 atttttctat ggctggattg ctaatcgagt atcaatgtga agtacctaat tttactgtgc 39660 attctactca agactgcaca gttacttcga cgtatagtga ggtagttgta aaagtttata 39720 ggtaagttat aggattgatt ggtaataatc tttaaatttt agggggggga ttgttcagat 39780 gtagtgtatt ctgtaaaata aaacttaatt atattttgct ttcaatacaa tgaacgatca 39840 agttttccaa ttacaaattg ttataaatgg aggtttaacc cccattcaat ctaagccaga 39900 aacacttgat aaattagtaa aagaatttgc tataaatcat ttgttgtttc caaaagaaat 39960 aactgaacaa ttaattgaga ttaattctca ggatggttct caaacaaaaa agataactaa 40020 atttattgat ttggttagta gcaatcaaaa atgtacctac caaattagaa atgattcact 40080 tgtattttta aattcctttg agaaaataga ggaattagaa agtatatttg aaaagttttt 40140 taaatcgttt tcggatctga ccccatatat aaactataaa caatcaaaaa gattggggct 40200 agttcttatt agggaggatt ataatgaggt tacattacgc gagtattgta cttcagaaga 40260 attagatcga aatgttattg agaatagatc gagaaaagtt actcgttttg ctatggcgga 40320 actaaatgaa atggtaaatt tatctgtttc aaaagattat gtaactcatg aatcaggagt 40380 ttctcgaaat actctagcaa gtgtttatga tgttaatacg ttatctacta aggatgtttt 40440 tagatttaca agtaaggatg tagtaaagtt tataaatgct tcaaagaaat ttattttaga 40500 atcaatgtaa gattttttat atgaactatt caaataattt atctaataat actatgtatg 40560 aaagtggtaa tcataaaaag ataatcacta agtacgagat tgaaacaata aaaacggttt 40620 ggcaaaccga taagatacaga tcttttttaa aagattactt aaatacagac gtagttagta 40680 ttactgaccc cactgttata gaacaaaaga taggggaaga gagcttaaag caaattaaaa 40740 gagaatttga tatttttaag aataaatttg ataattttct gagatatgaa gatgtgccag 40800 tcgattatgt ttcacctatt gaaaatgaat taatcaactt ttataaacat agtaaagttg 40860 aagttcaaga acaaattagc caatggatta ttgattcttt tgataacaca aaggttcttc 40920 ttaatatttt aaaaatttta ggtaatattg ctcctgattt tattgatcat caatttttaa 40980 ctaattttct tatcgttctt aatcataaag atactgaaat caaagaatat gcattaagaa 41040 ttcaagagaa attaatgctt ccatcatata ataatgtact gaagcactct aagttaactc 41100 caaaatggat tgatgactat agaaaagaat tggttgaatt gtatgaagaa gataataaag 41160 gtagttaatt taatatgact atttttgtaa gaaagataag taaagcaaaa tggccttctg 41220 aagaggaaat tgcagaaaaa gcactggatt cagaaattat accttttgtc agagccgatg 41280 ccttaactac ttgtttaaaa acttctcaaa atactttatc tgtttgggca gaaagattaa 41340 aagaaataaa ggcggtttaa ccgccttaaa ctgttgcaag ctgtgctgta ttaagcacag 41400 tcttgctttg ctcatatttc aaaacgtctt tctttttata tgaaacacgt ctcccaattt 41460 tcgagaaagg cagtgatgat tgatcacaac gcattctagc taatgtccaa ggcgagcaat 41520 ctaaataaag tgctacaacc tcttgaggaa acttctgttc ttcattagcc attatgaagc 41580 gatccaaata ttcttgttgc tctgcatcag atagatttct cagatctttt aacatttact 41640 cctccttact ttccgcttta acttctcgat caagacgctc aatctccgca attaataaag 41700 cggctgcacg aaccaaatct tgtcttgggc tttttggttt ccagaaagta tcagcaaaag 41760 gccaccatcc tgcagcatcc tcatccatat acacttcggg gccgaaatct ttgctgttat 41820 aaacccaacc tctacttact acatgatcaa cgtaacaaga tgcagctcgt ggcaattcat 41880 ttgcttcata gagattatca aattcaggta aatacccttc ttttataatt tggcgttctc 41940 tttcattaag aacatctttg acagcttgac tgctatataa ttcactcatc cctcagctcc 42000 cgattcgctt gccacttcaa ccatcaaaga ataaataggc gtgtaatgat cacgagtccc 42060 atcgccccaa tggaatccac tattttctaa acagctaaca acgctgtctg gaatctcttt 42120 cggcacaact acataaccct ctggcaccgc ctgagctttg gctttttcta gctctgcatc 42180 acgatgcttt gcacatctaa gccaagcatc ccaacggcta ttcatgttgc ttatttcttt 42240 ctgagcaatt tcagaaggat tgtttgatct agtcataaac agttcatgct catgactaaa 42300 aataatgtct cttcttcctt tgtaatattg gaaggtattc agaaaagcct ctctttcctt 42360 attcaaatca aacatcatta ggccctcaaa tattcttctt tagtccactc aacaaactct 42420 ttataaagct gctgcgcggg tttatttaac cggttgtgat agtcgatcgt tatgcggcgc 42480 caagcgactg gtaccgcata atgtttggtt agaaacattg cttgatccat gccttgccgg 42540 actattacgt agcccagcaa ttgcaagtag tacataaaac caagcatgtg tttttggctc 42600 actttcttgt actgatcttt catgttagaa accgtccact aataaataat cagggggaga 42660 ttcttgttga gtaggtgtag gattctctaa ttcatagcgg cgttttctca cataccccat 42720 tagcttcggt tgaatctgcg gatctcgtgc agccacgtct atttccaaag catctagcgt 42780 tgtaaggtct ggtgcagttt ggatttgaac cattaaagag ggtggctcat tagcagatgc 42840 cttttctttt tctagctctt caagacgttt gtgagtggcg agaaggatag gcttcatttg 42900 ttcgtcatcc catgtgcggg tataacgata aaccgcattt acttctgcag gtgtttttga 42960 ctcttttaca cgctgtagaa gagcatctaa tgccttctga tattcaggat ctactttagg 43020 ctcgttagtt tctggaacta acagatcctc agatgtggtg acatttgttt gttcggtaat 43080 aacaattgtt ggttgagttt ctgcagaaat aacgtcgcta ggcttttctg cttttgattt 43140 tttgcctcgc tgttttttgg gctcttcacc aaggcgaaca acgctaagat cattattaat 43200 ttcaaaaccg agtgcttttg aaaatgcttt taattgaagc ttggcatttt ctgcatcacg 43260 ttgaacaaat cctcttttaa tagcttcaat gagtgcagca gtttcaaatc ctatgatata 43320 aattgaaggg agatatgtat tgataacaaa aacatcctga cccgctttat actcatcaat 43380 agttaatggc tttgtgaatg taatgccagc cagttcaata gtttcgattt tgatgcagaa 43440 ttcaaaaccc ggtttgccaa aaacagaagc ggggaattga tctaagtcag aaaagtccaa 43500 catgtctcca ataggacgac aaagaacagt tttacctttt tgaagagcta caaatgcttc 43560 agctgcagtg attagattat tcatgctgtc atccccgttt tagctaatgt ttcaatgtct 43620 tgtttaactg ccttaagttt tgctgcttca atttgaataa gggcatcgat acctaagtgc 43680 tcacatactg tttttacgtc taggccacgt tcagcaataa agttttgaag ttcgtctctt 43740 tgttgatctg agataccgtt aaattctggt ggactaatcc aagtgccacg ttgtttatca 43800 aacgtgcaat tcaatgcttt agctctcatt aacattgctt gtcgcatgtt ctggtaatac 43860 atgtgttctt tatcaagcga ctcagttaat tgattaaggt cacctgcatg ctcagcttct 43920 tcacagcttt gtttccagtt ttctagctct tcttgggctt tagctgctgc aagttgtgca 43980 ggcgttaagg tgttaatgtg gtctttagct tgagtaatca ggtcagccaa gaaagtggga 44040 tgtgctttaa gatctggtac ccacacttca ccagtttcac cacctaaagc acctgagttt 44100 ttcgcatgat gtgtaggtga gggtttgaaa ttaataacgc gggcattttt accttcacca 44160 gtagtaacag ttgttagata acccatgaca tctgcgatac ggtaaagctc gttacggttt 44220 ttaccaccta gatctgggcg gtaaataatt tgatcaccgt tttgatcttc tgatgcgtgt 44280 gcaatgaaaa caacatcttt acctaaactg atcaaagtat tgatgtattg cttgaacgtt 44340 tggttcgcta aaccttgagc ctttaacttt aaagagccat ctttttgacg gttatttgcc 44400 gtaagtaaca gatgggtttt aatgcattca agcattgcac ccacggtatc aatgactacg 44460 gttttatatg gtgctaagtc ctgcggagta aggttagcta catcactcca ttgttgtacc 44520 tgtacgactg caccacgacg taattcacca gtacggtgag caccacggtc aaagtcaaaa 44580 gaaattgctt tttccgcagt aaagcccatc gatgatttac ctaaacccgg atccgcgtat 44640 aggtacacaa taattgcttg aaccaataaa gtttggtcag cagtaataat cggtagagcc 44700 attttcttat cctcatctag agccggtgaa gccgcgtttt tgcttatatg ctttgcggtc 44760 ataagtagga atgtttgttt cacgcagttt tattgcgagc tgctttctgc gttgaaagtc 44820 gatttcttgt gtgagttcat tccaaacttt tggatagtcg gtttgaaact tatacacatt 44880 taaaggcgtc ttaaatccgt ctttaacttt gtaaagaact gagccattag cattagatgc 44940 gtacacttgc cagccaatac gaacagagta gaggccctta tcatcacggc ctaaaaatga 45000 cttgtagccg tcggggtgct ttttgaaatg agtcatcttt aagcctcctt acattcgcat 45060 gtaccaacaa aggcatacgt aagcgggcta ggagcatcaa caggtgaaac gtccttaata 45120 tttaaaggaa taatttcttt gcgatattta actaaaacca catcaccttc acggcaattg 45180 acaattcctt ctcttgaaga aaaacgtgca gatttagaag attgggttac tctgcaaaat 45240 gaaacctcat caccagcttt gatttttgaa cggtcaacag gaatcatctt cttgcaagta 45300 gggcagttat aatctttcat taggctgcct ccaaccattt attacggtcg atatagcccg 45360 ctaa 45364

Claims (29)

항생제 내성 아시네토박터 균속에 대한 서열번호 1의 용균 효소를 암호화하는 핵산을 함유하는 용균성 박테리오파아지.A fungicidal bacteriophage comprising a nucleic acid encoding the lytic enzyme of SEQ ID NO: 1 for an antibiotic resistant Acinetobacter sp. 제 1항에 있어서,
상기 박테리오파아지는 기탁번호 KFCC11525P인 것을 특징으로 하는, 용균성 박테리오파아지.The method according to claim 1,
Wherein the bacteriophage is the accession number KFCC11525P. 제 1항에 있어서,
상기 박테리오파아지는 서열번호 2인 것을 특징으로 하는, 용균성 박테리오파아지.The method according to claim 1,
Wherein the bacteriophage is SEQ ID NO: 2. 제 1항에 있어서,
상기 항생제 내성 아시네토박터 균속은 Acinetobacter baumannii , Acinetobacter calocoaceticus , Acinetobacter haemolyticus , Acinetobacter junii, Acinetobacter johnsonii , Acinetobacter lwoffii , Acinetobacter radioresistens 중에서 선택하는 어느 하나인 것을 특징으로 하는, 용균성 박테리오파아지.The method according to claim 1,
The antibiotic-resistant Acinetobacter is Acinetobacter Species baumannii , Acinetobacter calocoaceticus , Acinetobacter haemolyticus , Acinetobacter junii, Acinetobacter johnsonii , Acinetobacter lwoffii , and Acinetobacter radioresistens . & lt ; RTI ID = 0.0 & gt ; 21. & lt ; / RTI &gt; 제 1항에 있어서,
상기 항생제는 카바페넴인 것을 특징으로 하는, 용균성 박테리오파아지.The method according to claim 1,
Wherein the antibiotic is carbapenem. 제 1항에 있어서,
　상기 항생제 내성 아시네토박터 균속이 생산하는 효소는 카바페넴아제인 것을 특징으로 하는, 용균성 박테리오파아지.The method according to claim 1,
Wherein the enzyme produced by the antibiotic-resistant Acinetobacter sp. Is carbapenemase. 제 1항에 있어서,
상기 항생제 내성 아시네토박터 균속이 생산하는 카바페넴아제는 OXA형인 것을 특징으로 하는, 용균성 박테리오파아지.The method according to claim 1,
Wherein the carbapenemase produced by the antibiotic-resistant Acinetobacter sp. Is the OXA type. 서열번호 1로 표시되는 폴리펩타이드.1. A polypeptide represented by SEQ ID NO: 1. 서열번호 1로 표시되는 폴리펩타이드를 암호화하는 핵산분자.A nucleic acid molecule encoding the polypeptide represented by SEQ ID NO: 1; 제 8항의 핵산분자를 포함하는 재조합 벡터.9. A recombinant vector comprising the nucleic acid molecule of claim 8. 제 9항의 재조합벡터로 형질전환된 미생물.A microorganism transformed with the recombinant vector of claim 9. 항생제 내성 아시네토박터 균속에 대한 서열번호 1의 용균 효소를 함유하는 용균성 박테리오파아지를 유효성분으로 포함하는 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물.1. A pharmaceutical composition for the treatment of diseases caused by antibiotic resistant Asnithobacter sp. Containing as an active ingredient a fungicidal bacteriophage containing the lytic enzyme of SEQ ID NO: 1 against an antibiotic resistant Ashantobacter sp. 제 12항에 있어서,
　상기 용균성 박테리오파아지는 기탁번호 KFCC11525P인 것을 특징으로 하는,　항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물.13. The method of claim 12,
The pharmaceutical composition for the treatment of diseases caused by antibiotic-resistant Acinetobacter sp. KFCC11525P, wherein said fungus bacteriophage is deposited at KFCC11525P. 제 12항에 있어서,
상기 용균성 박테리오파아지는 서열번호 2인 것을 특징으로 하는,　항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물.13. The method of claim 12,
Wherein said phytotoxic bacteriophage is SEQ ID NO: 2. 2. A pharmaceutical composition for the treatment of diseases caused by antibiotic resistant Asnithobacter sp. 제 12항에 있어서,
상기 질환은 C형 간염, 수족구병, 임질, 클라미디아, 연성하감, 성기단순포진, 첨규콘딜롬, 반코마이신내성황색포도알균감염증, 반코마이신내성장알균감염증, 메티실린내성황색포알균감염증, 다제내성녹농균감염증, 다제내성아시네토박터바우마니균감염증, 카바페넴내성장내속균종감염증, 장관감염증, 급성호홉기감염증, 엔테로바이러스감염증 중에서 선택하는 어느 하나인 것을 특징으로 하는, 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물.13. The method of claim 12,
The disease may be selected from the group consisting of hepatitis C, genital warts, gonorrhea, chlamydia, soft hypersensitivity, genital herpes zosteracin, dilacillum vancomycin-resistant Staphylococcus aureus infections, growth vancomycinemia infections, methicillin- Wherein the infection is caused by an antibiotic-resistant Acinetobacter spp., Characterized in that the agent is any one selected from the group consisting of a bacterial infection with Aspergillus niger, a bacterial infection with Aspergillus niger, a carbapenem resistant intestinal microflora, a vesicular infection, acute respiratory infections and an enterovirus infection &Lt; / RTI &gt; 제 12항에 있어서,
상기 항생제는 카바페넴인 것을 특징으로 하는, 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물.13. The method of claim 12,
A pharmaceutical composition for the treatment of a disease caused by antibiotic-resistant Acinetobacter sp., Wherein the antibiotic is carbapenem. 제 12항에 있어서,
상기 항생제 내성 아시네토박터 균속이 생산하는 효소는 카바페넴아제인 것을 특징으로 하는, 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물.13. The method of claim 12,
A pharmaceutical composition for the treatment of a disease caused by antibiotic-resistant Acinetobacter sp., Wherein the enzyme produced by said antibiotic-resistant Acinetobacter sp. Is carbapenemase. 제 17항에 있어서,
상기 카바페넴아제는 OXA-형인 것을 특징으로 하는, 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물.18. The method of claim 17,
Wherein the carbapenemase is of the OXA-type. &Lt; Desc / Clms Page number 19 &gt; 제 8항의 폴리펩타이드를 유효성분으로 포함하는 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물.9. A pharmaceutical composition for the treatment of a disease caused by antibiotic resistant Asnithobacter sp. Containing the polypeptide of claim 8 as an active ingredient. 제 19항에 있어서,
상기 질환은 C형 간염, 수족구병, 임질, 클라미디아, 연성하감, 성기단순포진, 첨규콘딜롬, 반코마이신내성황색포도알균감염증, 반코마이신내성장알균감염증, 메티실린내성황색포알균감염증, 다제내성녹농균감염증, 다제내성아시네토박터바우마니균감염증, 카바페넴내성장내속균종감염증, 장관감염증, 급성호홉기감염증, 엔테로바이러스감염증 중에서 선택하는 어느 하나인 것을 특징으로 하는, 제 8항의 폴리펩타이드를 유효성분으로 포함하는 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물.20. The method of claim 19,
The disease may be selected from the group consisting of hepatitis C, genital warts, gonorrhea, chlamydia, soft hypersensitivity, genital herpes zosteracin, dilacillum vancomycin-resistant Staphylococcus aureus infections, growth vancomycinemia infections, methicillin- , Multidrug-resistant Acinetobacter baumannii infection, carbapenem-resistant intestinal microflora infectious disease, intestinal infectious disease, acute respiratory infectious disease, and enterovirus infection, wherein the polypeptide of claim 8 is used as an effective ingredient A pharmaceutical composition for the treatment of a disease caused by an antibiotic-resistant Acinetobacter sp. 제 19항에 있어서,
상기 항생제는 카바페넴인 것을 특징으로 하는, 제 8항의 폴리펩타이드를 유효성분으로 포함하는 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물.20. The method of claim 19,
9. A pharmaceutical composition for the treatment of a disease caused by antibiotic-resistant Acinetobacter sp. Containing the polypeptide of claim 8 as an active ingredient, wherein the antibiotic is carbapenem. 제 21항에 있어서,
상기 항생제 내성 아시네토박터 균속이 생산하는 효소는 카바페넴아제인 것을 특징으로 하는, 제 8항의 폴리펩타이드를 유효성분으로 포함하는 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 치료용 약학 조성물.22. The method of claim 21,
A pharmaceutical composition for the treatment of a disease caused by an antibiotic-resistant Acinetobacter sp. Containing the polypeptide of claim 8 as an active ingredient, wherein the enzyme produced by said antibiotic-resistant Acinetobacter sp. Is carbapenemase. 항생제 내성 아시네토박터 균속에 대한 서열번호 1의 용균 효소를 함유하는 용균성 박테리오파아지 또는 서열번호 1의 용균 효소를 유효성분으로 포함하는 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 개선용 식품 조성물.A phytotoxic bacteriophage containing the lytic enzyme of SEQ. ID. NO: 1 for antibiotic resistant Ashantobacter sp. Or a food composition for improving disease caused by antibiotic resistant Ashantobacterium sp. Containing the lytic enzyme of SEQ. . 제 23항에 있어서,
상기 용균성 박테리오파아지는 기탁번호 KFCC11525P인 것을 특징으로 하는,　항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 개선용 식품 조성물.24. The method of claim 23,
The food composition for improving diseases caused by antibiotic resistant Asnitococcus spp., Wherein the phytotoxic bacteriophage is deposited at KFCC11525P. 제 23항에 있어서,
상기 용균성 박테리오파아지는 서열번호 2인 것을 특징으로 하는, 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 개선용 식품 조성물.24. The method of claim 23,
Wherein said phytotoxic bacteriophage is SEQ ID NO: 2. 2. A food composition for improving diseases caused by antibiotic resistant Asnitobacter sp. 제 23항에 있어서,
상기 질환은 C형 간염, 수족구병, 임질, 클라미디아, 연성하감, 성기단순포진, 첨규콘딜롬, 반코마이신내성황색포도알균감염증, 반코마이신내성장알균감염증, 메티실린내성황색포알균감염증, 다제내성녹농균감염증, 다제내성아시네토박터바우마니균감염증, 카바페넴내성장내속균종감염증, 장관감염증, 급성호홉기감염증, 엔테로바이러스감염증 중에서 선택하는 어느 하나인 것을 특징으로 하는, 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 개선용 식품 조성물.24. The method of claim 23,
The disease may be selected from the group consisting of hepatitis C, genital warts, gonorrhea, chlamydia, soft hypersensitivity, genital herpes zosteracin, dilacillum vancomycin-resistant Staphylococcus aureus infections, growth vancomycinemia infections, methicillin- Wherein the infection is caused by an antibiotic-resistant Acinetobacter spp., Characterized in that the agent is any one selected from the group consisting of a bacterial infection with Aspergillus niger, a bacterial infection with Aspergillus niger, a carbapenem resistant intestinal microflora, a vesicular infection, acute respiratory infections and an enterovirus infection Wherein the food composition is a food composition. 제 23항에 있어서,
상기 항생제는 카바페넴인 것을 특징으로 하는, 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 개선용 식품 조성물.24. The method of claim 23,
Wherein the antibiotic is carbapenem. 2. The food composition according to claim 1, wherein the antibiotic is carbapenem. 제 23항에 있어서,
상기 항생제 내성 아시네토박터 균속이 생산하는 효소는 카바페넴아제인 것을 특징으로 하는, 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 개선용 식품 조성물.24. The method of claim 23,
The food composition for improving diseases caused by antibiotic resistant Asnitococcus spp., Wherein the enzyme produced by the antibiotic-resistant Acinetobacter sp. Is carbapenemase. 제 28항에 있어서,
상기 카바페넴아제는 OXA-형인 것을 특징으로 하는, 항생제 내성 아시네토박터 균속에 의해 유발되는 질환의 개선용 식품 조성물.




29. The method of claim 28,
Wherein the carbapenemase is of the OXA-type. &Lt; RTI ID = 0.0 &gt; 11. &lt; / RTI &gt;




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