KR102646232B1 - 항생제 내성 슈도모나스균 특이적 박테리오파지 - Google Patents
항생제 내성 슈도모나스균 특이적 박테리오파지 Download PDFInfo
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- KR102646232B1 KR102646232B1 KR1020210136865A KR20210136865A KR102646232B1 KR 102646232 B1 KR102646232 B1 KR 102646232B1 KR 1020210136865 A KR1020210136865 A KR 1020210136865A KR 20210136865 A KR20210136865 A KR 20210136865A KR 102646232 B1 KR102646232 B1 KR 102646232B1
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- bacteriophage
- pseudomonas aeruginosa
- seq
- ymc17
- pae
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Abstract
본 발명은 항생제에 내성을 나타내는 슈도모나스 균속을 용균시키는 박테리오파지에 관한 것이다. 구체적으로, 상기 슈도모나스 균속은 녹농균 (Pseudomonas aeruginosa)에 관한 것일 수 있다.
Description
본 발명은 항생제에 내성을 나타내는 슈도모나스 균을 용균시키는 박테리오파지에 관한 것이다. 구체적으로, 상기 슈도모나스 균은 녹농균 (Pseudomonas aeruginosa)에 관한 것일 수 있다.
과거 1960년대와 1970년대 초반까지 항생제 개발에 괄목할 만한 많은 성과가 있었고, 이를 통하여 많은 감염증이 치료되었다. 그러나 여전히 감염병의 심각성을 줄어들지 않고 있다.
항생제가 박테리아에 의한 감염성 질환에 있어 주된 치료 방법으로 지속적으로 이용되고 있으나, 과도한 항생제의 사용으로 인하여 1980년대부터 많은 항생제 내성 균주가 발생하기 시작했으며, 기존 항생제로는 효과적 치료를 기대할 수 없는 일명 슈퍼박테리아(super-bacteria) 또는 슈퍼버그(super-bug)라 불리는 내성균(resistant bacteria)까지 발생하여 큰 문제로 대두되고 있다.
이처럼 내성균이 증가하게 된 주된 원인으로는 무분별한 항생제 오남용(mis- and over-use)으로 인한 사람, 가축, 야생동물, 양식어류, 토양, 하천, 바다 등 환경 전체의 항생제 오염을 들 수 있다. 항생제 과다 사용이 새롭게 개발된 항생제에 대한 박테리아의 내성 획득 시간을 과거보다 더 짧게 만드는 하나의 원인이 되고 있는 것이다. 그러나 보다 더 근본적인 원인은 새롭게 개발된 합성 항생제 대부분이 과거 개발된 항생제의 기본 골격 구조를 그대로 유지하면서 화학적으로 약간의 구조만을 변경시키는 방식으로 개발되고 있는 기술적 한계에 기인하고 있다.
현재 시장에 나와 있는 모든 항생제는 내성 문제에 직면하고 있으며, 이에 따라 기존 항생제의 내성 문제에서 자유로운 새로운 계열(class)의 항생제의 개발 및 기존 항생제의 사용에서 나타나던 여러 부작용(side effect)이나 문제점을 개선할 수 있는 기술에 대한 요구가 지속되고 있다.
본 발명의 목적은 항생제 내성 녹농균(Pseudomonas aeruginosa)에 특이적인 사멸능을 가지는 박테리오파지를 제공하는 것이다.
본 발명의 다른 목적은 상기 박테리오파지를 포함하는 항생제를 제공하는 것이다.
본 발명의 또 다른 목적은 상기 박테리오파지를 포함하는 소독제를 제공하는 것이다.
본 발명의 또 다른 목적은 상기 박테리오파지를 포함하는 녹농균 유발 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.
본 발명의 또 다른 목적은 상기 박테리오파지를 포함하는 식품 조성물을 제공하는 것이다.
본 발명의 또 다른 목적은 상기 박테리오파지를 포함하는 사료 조성물을 제공하는 것이다.
상기와 같은 목적을 달성하기 위한 본 발명의 일 측면은 항생제 내성 녹농균(Pseudomonas aeruginosa)에 특이적인 사멸능을 가지는 박테리오파지에 관한 것이다.
본 발명에서, “박테리오파지(Bacteriophage)"는 박테리아를 감염시켜 성장을 억제하고 저해하는 박테리아 특이적 바이러스로 파지(phage)로 불리기도 한다. 박테리오파지는 핵산으로 이루어진 유전물질 중심부를 단백질 외피가 싸고 있는 단순한 구조의 유기체이며, 핵산은 단일 사슬이거나 이중 사슬인 DNA 또는 RNA로 되어있다. 박테리오파지는 생존에 숙주(host)가 반드시 필요하며, 박테리아의 세포벽(cell wall)의 펩티도글리칸(peptidoglycan) 층(layer)을 공격하여 세포벽을 파괴함으로써 박테리아를 사멸시킬 수 있다.
박테리오파지의 가장 큰 특징으로는, 감염성 박테리아 속에 침투한 다음 박테리아의 세포벽을 파괴하여 박테리아의 사멸을 유도한다는 것이며, 이러한 박테리오파지에 의한 세포 사멸의 기작은 세균의 세포벽 합성을 방해하는 방식의 기존 합성 항생제의 기작과는 완전히 다르다. 따라서 기존 합성 항생제에 대한 감수성에 관계없이 자신의 항균 활성을 발휘할 수 있다. 이로 인하여 특히 기존 항생제에 대하여 이미 내성을 획득한 내성균에 대해서도 항균 효과가 있다. 또한, 박테리아에 대해서는 매우 특이적인 항균 활성을 가지고 있기 때문에 인간을 포함한 동물을 구성하는 세포인 진핵세포(eukaryotic cell)에는 영향을 주지 않는다는 장점을 가진다.
슈도모나스 균속(Pseudomonas spp.)은 그람 음성 간균으로 포도당 비발효 세균이다. 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 고위험군 환자에서의 내인성 기회감염을 일으키는 중요한 병원성 세균이다.
슈도모나스 균속 중 하나인 녹농균(Pseudomonas aeruginosa)은 달콤한 냄새의 녹색을 띠는 농을 생산하며, 토양이나 물속 등 자연계에 광범위하게 존재하는 세균으로, 강한 병원성 균에 해당한다. 녹농균은 신체의 거의 모든 조직을 감염시킬 수 있으며, 감염 부위의 조직을 손상시키면서 고름이 나올 수 있고, 감염된 부위 및 질병에 따라 기침, 호흡 곤란, 체중 감소, 각막 궤양, 피로 등을 일으키며, 녹농균이 국소 부위에 감염되었다가 혈류를 통해 전신에 전파되면 패혈증을 일으키게 된다.
이러한 녹농균은 동물과 식물에 질병을 일으킬 수 있는 기회성 병원체(opportunistic pathogen)이나, 각종 항생제에 높은 내성을 나타내기 때문에 녹농균에 감염되면 특효적 치료제가 적어 중증이 되는 경우가 발생한다.
본 발명에서, "항생제 내성"은 특정 항생제에 내성을 보여 약효가 듣지 않는 것을 의미한다. 구체적으로, 상기 항생제는 카바페넴(carbapenem) 계열일 수 있다.
상기 카바페넴(carbapenem)은 그 항균 범위가 가장 넓고, ESBL이나 AmpC β-락타마제를 포함한 클래스 A, D 및 D β-락타마제에 안정한 가장 강력한 β-락탐 항균제에 해당한다. 그런데 현재 국내뿐만 아니라 세계적으로 카바페넴(carbapenem) 제제조차 내성을 보이는 다제 내성(multidrug resistant) 슈도모나스 균속에 의한 감염이 증가하고 있어서 임상적으로 커다란 문제가 되고 있다.
더욱 구체적으로, 상기 카바페넴(carbapenem) 계열 항생제는 아미카신(amikacin), 아제트레오남(azetreonam), 세프타지딤(ceftazidime), 시프로플록사신(ciprofloxacin), 콜리스틴(colistin), 세페핌(cefepime), 젠타마이신(gentamicin), 이미페넴(imipenem), 레보플록사신(levofloxacin), 메로페넴(meropenem), 피페라실린(piperacillin), 피페라실린-타조박탐(piperacillin-tazobactam) 및 이들의 조합으로 이루어진 군에서 선택되는 하나 이상일 수 있으나, 이에 제한되는 것은 아니다.
또한 구체적으로, 상기 박테리오파지는 서열번호 8의 염기 서열로 이루어진 유전체를 포함하는 것일 수 있다. 상기 서열번호 8의 염기 서열로 이루어진 유전체는 용균 효소(lytic enzyme)로서 키티네이즈 도메인을 포함하는 용균성 관련 단백질을 발현시킬 수 있는 바, 이를 포함함으로써 녹농균에 대한 용균성을 발휘할 수 있다.
나아가, 본 발명의 박테리오파지는 서열번호 8로 표시되는 염기 서열, 및 상기 염기 서열의 기능적 동등물을 포함할 수 있다. 상기 기능적 동등물이란 염기 서열의 변형, 치환의 결과, 상기 서열번호 8로 표시되는 염기 서열과 적어도 70% 이상, 바람직하게는 80% 이상, 더욱 바람직하게는 90% 이상, 가장 바람직하게는 95% 이상의 서열 상동성을 갖는 것으로, 서열번호 8로 표시되는 염기 서열과 실질적으로 동질의 생리활성을 나타내는 서열을 의미한다.
더욱 구체적으로, 상기 박테리오파지는 서열번호 2 내지 7, 서열번호 9 내지 23중 적어도 하나 이상의 염기 서열로 이루어진 유전체를 더욱 포함하는 것일 수 있다. 상기 서열번호 2 내지 7, 서열번호 9 내지 23각각은 상기 박테리오파지의 ORF(Open reading frame)의 염기 서열로서 상기 서열번호 8의 염기서열로 이루어진 용균성 관련 유전체에 더하여 추가로 포함될 수 있으나, 이에 제한되는 것은 아니다.
또한 구체적으로, 상기 박테리오파지는 서열번호 1로 염기서열로 이루어진 유전체를 포함하는 것일 수 있다.
나아가, 본 발명의 박테리오파지는 서열번호 1로 표시되는 염기 서열, 및 상기 염기 서열의 기능적 동등물로 이루어질 수 있다. 상기 기능적 동등물이란 염기 서열의 변형, 치환의 결과, 상기 서열번호 1로 표시되는 염기 서열과 적어도 70% 이상, 바람직하게는 80% 이상, 더욱 바람직하게는 90% 이상, 가장 바람직하게는 95% 이상의 서열 상동성을 갖는 것으로, 서열번호 1로 표시되는 염기 서열과 실질적으로 동질의 생리활성을 나타내는 서열을 의미한다.
또한 구체적으로, 상기 박테리오파지는 2021년 2월 26일 한국미생물보존센터(KCCM)에 기탁번호 KCCM12962P로 기탁된 것일 수 있다.
또한 구체적으로, 상기 박테리오파지는 포도비리대(Podoviridae)에 속하는 것일 수 있으며, 이는 육각형 머리에 짧은 꼬리를 가지는 것일 수 있다.
본 발명의 다른 측면은 상기 박테리오파지를 포함하는 항생제에 관한 것이다.
상기 항생제는 종래의 항균제, 살균제, 방부제 등을 모두 포함하며, 대부분의 항생 물질이 균주의 내성이 증가함에 따라 사용범위가 감소하는 반면, 본 발명의 상기 항생제는 균주의 내성과 관계없이 적용이 가능한 바, 지속적으로 사용 가능하다.
본 발명의 또 다른 측면은 상기 박테리오파지를 포함하는 소독제에 관한 것이다. 본 발명의 소독제는 항생제 내성 녹농균에 대해 특이적 사멸능을 가지는 박테리오파지를 포함하는 바, 병원에서의 감염을 방지하기 위한 병원 및 보건용 도구 등의 소독제로 유용하게 사용될 수 있고, 일반 생활 소독제, 식품 및 조리 장소 및 설비의 소독제, 축산 산업의 축사 소독제로 유용하게 사용될 수 있다.
본 발명의 또 다른 측면은 상기 박테리오파지를 포함하는, 녹농균 유발 질환의 예방 또는 치료용 약학적 조성물에 관한 것이다. 본 발명의 상기 박테리오파지는 슈도모나스속 균, 특히 카바페넴 계열 항생제에 내성을 가지는 녹농균을 특이적으로 사멸시키는 바, 이러한 녹농균에 의해 유발되는 다양한 질환에 대해 예방 및/또는 치료 효과를 나타낼 수 있다.
구체적으로, 상기 녹농균 유발 질환은 폐렴, 패혈증, 뇌수막염, 균혈증, 심내막염, 복막염 또는 내인성 기회감염인 것일 수 있으나, 이에 제한되는 것은 아니다. 녹농균은 자연계에 광범위하게 존재하는 강한 병원성 균으로서 신체의 거의 모든 조직을 감염시킬 수 있는 바, 상기 질환 외에도 신체 여러 부위에서 녹농균에 의해 발생되는 모든 감염성 질환을 포함한다.
본 발명의 또 다른 측면은 상기 약학적 조성물을 개체에 투여하는 단계를 포함하는, 녹농균 유발 질환의 치료방법에 관한 것이다.
'녹농균 유발 질환'은 상기 설명한 바와 같다.
본 발명의 용어 "개체"는 본 발명에 따른 약학적 조성물의 투여에 의해 증상이 호전될 수 있는 녹농균 유발 질환을 가진 동물 또는 인간을 포함한다. 본 발명에 따른 치료용 조성물을 개체에게 투여함으로써, 녹농균 유발 질환을 효과적으로 예방 및 치료할 수 있다.
본 발명의 용어 "투여"는 어떠한 적절한 방법으로 인간 또는 동물에게 소정의 물질을 도입하는 것을 의미하며, 본 발명에 따른 치료용 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 경구 또는 비경구 투여될 수 있다. 또한, 본 발명에 따른 치료용 조성물은 유효성분이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수 있다.
본 발명에 따른 약학적 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다.
본 발명의 또 다른 측면은 상기 박테리오파지를 포함하는, 식품 조성물에 관한 것이다. 더욱 구체적으로 상기 식품 조성물은 녹농균 유발 질환의 예방 또는 개선용 식품 조성물인 것일 수 있다.
상기 식품의 종류에는 특별한 제한은 없다. 본 발명의 조성물을 첨가할 수 있는 식품은 소세지, 육류, 빵, 초콜릿류, 스넥류, 캔디류, 과자류, 라면, 피자, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있다. 음료수로 제형화할 경우에 본 발명의 조성물 외에 첨가되는 액체 성분으로는 이에 한정되지는 않으나, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 모노사카라이드(예, 포도당, 과당 등), 디사카라이드(예, 말토오스, 수크로오스 등) 및 폴리사카라이드(예, 덱스트린, 시클로덱스트린 등과 같은 통상적인 당), 및 자일리톨, 소르비톨, 에리스리톨 등의 당 알코올일 수 있다.
상기 식품의 종류는 구체적으로 건강기능식품일 수 있다. 상기 건강기능 식품은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 증진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 유기산, 보호성 콜로이드 점증제, pH 조절제, 안정화제, 보존제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 또한, 본 발명의 건강기능 식품은 과일 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 단독으로 또는 조합으로 사용될 수 있다.
상기 건강기능식품은 식품의 생체 조절 기능을 강조한 식품으로 물리적, 생화학적, 생물공학적인 방법을 이용하여 특정 목적에 작용 및 발현하도록 부가가치를 부여한 식품이다. 이러한 건강기능 식품의 성분은 생체 방어와 신체 리듬의 조절, 질환의 방지 및 회복에 관계하는 신체 조절 기능을 생체에 대하여 충분히 발휘하도록 설계하여 가공하게 되며, 식품으로 허용 가능한 식품 보조 첨가제, 감미료 또는 기능성 원료를 함유할 수 있다.
본 발명의 조성물을 건강기능식품(또는 건강기능 음료 첨가물)으로 사용할 경우, 상기 조성물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용하고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 상기 조성물의 혼합량은 그의 사용 목적(예방, 건강 또는 개선, 치료적 처치)에 따라 적합하게 결정될 수 있다.
본 발명의 또 다른 측면은 상기 박테리오파지를 포함하는 사료 첨가용 조성물에 관한 것이다. 축산업이나 수산업에서 사용되는 사료 첨가용 항생제는 질병의 예방 목적으로 사용되고 있는데, 예방 목적의 항생제 투여는 내성균 발생 가능성을 높이고 가축에 잔류하는 항생제가 사람에게 전달될 수 있어서 문제가 되었으며, 항생제가 육류를 통해 인체에 흡수되면 항생제 내성을 유발해 질병의 확산을 부를 수도 있다. 또한, 사료에 섞여 먹이는 항생제의 종류가 많고 이는 다제 내성균 발생 확률이 높아지는 문제점이 있어 자연 친화적이면서도 기존 항생제의 사용에서 발생한 문제를 해결할 새로운 사료 첨가용 항생물질로서 본 발명의 상기 박테리오파지를 이용할 수 있다.
본 발명의 또 다른 측면은 상기 박테리오파지를 포함하는 사료 조성물에 관한 것이다. 본 발명의 사료는 박테리오파지를 사료 첨가제 형태로 따로 제조하여 사료에 혼합시키거나, 사료 제조 시 직접 첨가하여 제조할 수 있다. 본 발명의 사료 내 박테리오파지는 액상 또는 건조상태일 수 있다. 건조방법은 통풍건조, 자연건조, 분무건조 및 동결건조가 가능하지만, 이에 제한되는 것은 아니다.
또한, 상기 사료는 본 발명의 박테리오파지 외에 사료의 보존성을 높일 수 있는 통상의 첨가제들을 추가로 포함할 수 있다.
본 발명의 박테리오파지를 포함하는 사료에는 식물성으로는 곡물류, 근과류, 식품가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류, 곡물부산물류 등이 있으며, 동물성으로는 단백질류, 무기물류, 유지류, 광물성류, 유지류, 단세포 단백질, 동물성 플랑크톤류, 남은 음식물 등이 있으며 이에 제한되는 것은 아니다.
본 발명의 사료 첨가용 조성물에는 품질 저하를 방지하기 위하여 첨가하는 결착제, 유화제, 보존제 등이 포함될 수 있고, 효용 증대를 위하여 사료에 첨가하는 아미노산제, 비타민제, 효소제, 생균제, 향미제, 비단백태질소화합물, 규산염제, 완충제, 착색제, 추출제, 올리고당 등이 포함될 수 있으며, 그 외에도 사료 혼합제 등을 추가로 포함할 수 있다.
본 발명에서 제공하는 신규한 박테리오파지는 기존의 항생제에 비해 항생제에 내성을 갖는 녹농균에 대하여 특이적 사멸능을 가진다.
나아가 사람, 동물, 식물 등 세균외의 다른 숙주는 감염시키지 않으므로, 항생제 오남용으로 인한 항생제 내성균의 문제점, 식품 내의 항생제의 잔류 문제, 광범위한 숙주범위의 문제점을 해결할 수 있다.
본 발명의 효과는 상기한 효과로 한정되는 것은 아니며, 본 발명의 상세한 설명 또는 청구범위에 기재된 발명의 구성으로부터 추론 가능한 모든 효과를 포함하는 것으로 이해되어야 한다.
도 1은 본 발명에 따른 박테리오파지 YMC17/07/R4900a_PAE_BP의 전자 현미경 촬영 사진을 나타낸 것이다.
도 2는 본 발명에 따른 박테리오파지 YMC17/07/R4900a_PAE_BP의 항생제 내성을 갖는 녹농균에 대한 흡착능을 그래프로 나타낸 것이다.
도 3은 본 발명에 따른 항생제 내성을 갖는 녹농균에 대한 박테리오파지 YMC17/07/R4900a_PAE_BP의 1단 증식 곡선을 그래프로 나타낸 것이다.
도 4는 본 발명에 따른 박테리오파지 YMC17/07/R4900a_PAE_BP의 생체 외에서 항생제 내성을 갖는 녹농균에 대한 용균능을 그래프로 나타낸 것이다.
도 5는 본 발명에 따른 항생제 내성을 갖는 녹농균에 대한 박테리오파지 YMC17/07/R4900a_PAE_BP의 온도 안정성을 그래프로 나타낸것이다.
도 6은 본 발명에 따른 항생제 내성을 갖는 녹농균에 대한 박테리오파지 YMC17/07/R4900a_PAE_BP의 pH 안정성을 그래프로 나타낸 것이다.
도 7은 본 발명에 따른 박테리오파지 YMC17/07/R4900a_PAE_BP의 전체 유전체 서열 분석 결과를 나타낸 것이다.
도 2는 본 발명에 따른 박테리오파지 YMC17/07/R4900a_PAE_BP의 항생제 내성을 갖는 녹농균에 대한 흡착능을 그래프로 나타낸 것이다.
도 3은 본 발명에 따른 항생제 내성을 갖는 녹농균에 대한 박테리오파지 YMC17/07/R4900a_PAE_BP의 1단 증식 곡선을 그래프로 나타낸 것이다.
도 4는 본 발명에 따른 박테리오파지 YMC17/07/R4900a_PAE_BP의 생체 외에서 항생제 내성을 갖는 녹농균에 대한 용균능을 그래프로 나타낸 것이다.
도 5는 본 발명에 따른 항생제 내성을 갖는 녹농균에 대한 박테리오파지 YMC17/07/R4900a_PAE_BP의 온도 안정성을 그래프로 나타낸것이다.
도 6은 본 발명에 따른 항생제 내성을 갖는 녹농균에 대한 박테리오파지 YMC17/07/R4900a_PAE_BP의 pH 안정성을 그래프로 나타낸 것이다.
도 7은 본 발명에 따른 박테리오파지 YMC17/07/R4900a_PAE_BP의 전체 유전체 서열 분석 결과를 나타낸 것이다.
이하, 본 발명을 실시예에 의해 상세히 설명한다. 단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명이 하기 실시예에 의해 한정되는 것은 아니다.
실시예 1. 임상검체 분리 및 항생제 내성 균주 선별
하기 표 1과 같이 세브란스 병원 환자들의 객담과 임상 검체로부터 녹농균(Pseudomonas aeruginosa)을 분리하여 배양하였다. 균주 동정은 키트 ATB 32 GN 시스템(bioMerieux, Marcyl'Etoile, France)을 이용하여 수행하였다.
[표 1]
이후, 카바페넴 계열인 아미카신(amikacin), 아제트레오남 (azetreonam), 세프타지딤(ceftazidime), 시프로플록사신(ciprofloxacin), 콜리스틴(colistin), 세페핌(cefepime), 젠타마이신(gentamicin), 이미페넴(imipenem), 레보플록사신(levofloxacin), 메로페넴(meropenem), 피페라실린(piperacillin), 및 피페라실린-타조박탐(piperacillin-tazobactam)을 시험 항생제로 하고, 뮬러-힌튼(Mueller-Hinton) 아가를 사용하여 외기 37 ℃에서 하룻밤 동안 배양하는 CLSI 디스크 확산 시험 방법을 이용하여 항생제 감수성 시험을 수행하였다. 감수성 결과는 Clinical and Laboratory Standards Institute(CLSI, 2016)를 기준으로 판독하였다.
그 결과, 수집된 녹농균(Pseudomonas aeruginosa) 균주는 다양한 항생제에 대하여 내성을 가지는 다재내성 균주임을 확인하였으며, 하기 표 2의 항생제 내성 프로파일에 나타난 바와 같이 수집된 녹농균(Pseudomonas aeruginosa) 중 46개 균주가 카바페넴에 대한 내성을 나타내었다. 표 2에서 S, I 및 R은 항균제에 대한 감수성을 평가한 결과로, 'S'는 민감(Susceptible), 'I'는 중간(Intermediate), 'R'은 내성(Resistant)를 의미한다.
[표 2]
실시예 2. 용균성 파지 선별 및 용균역가 측정
2-1. 박테리오파지 분리를 위한 검체 수집
세브란스 병원의 오수 처리시설에서 최초 침전지를 거친 후 부유물질 및 침사물이 제거된 처리수 2 L를 채취하였다. 이는 화학 처리 시설 전 단계의 오수로 제한하였다. 수집한 시료에 1 L당 염화나트륨 58 g을 첨가한 후 10,000 g에서 10 분간 원심 분리하여 200 nm 밀리포어 필터로 여과하였다. 얻어진 여과액에 폴리에틸렌글리콜(PEG, 분자량 8000)을 10 %(w/v)으로 첨가하고 4 ℃에서 12 시간 동안 냉장보관하였다. 12 시간 냉장 보관된 여과액을 15,000 g에서 60 분간 원심 분리하여 침전물을 파지 희석 완충액 (sodium-magnesium (SM) 완충액)에 재부유하여 최종 300 mL의 박테리오파지 부유액을 채취하였다.
2-2. 박테리오파지 정제
용균성 파지의 분리 정제는 스팟 테스트(Spot Test)법)으로 실행하였다. 구체적으로, 표 1에서 확보된 균주를 맥콘키 한천배지에서 접종 후 외기 37 ℃에서 하룻밤 동안 배양하였다. 배양 후, 투명한 플라크 형성을 확인하고 파지에 감수성인 균주를 선별하였다. 감수성인 균주를 맥콘키 한천 배지에 접종하여 37 ℃에서 12 시간 동안 배양하였다. 탑 아가(4 mL)에 감수성 균주 40 μL 및 파지 용액(각각 1 μL, 10 μL 및 50 μL)을 섞어 LB 아가에 도포한 후, 37 ℃에서 12시간 동안 배양하였다. 단일 플라크가 관찰된 아가 플레이트에서 멸균 파이펫팁으로 플라크를 채취하여 SM 완충 용액에 희석하고, 다시 감수성인 균주 현탁액을 이용하여 3회 반복 정제하였다. 이렇게 순수한 박테리오 파지를 수득하였으며, 이를 YMC17/07/R4900a_PAE_BP로 명명하고, SM 완충 용액에 희석하여 보관하였다.
상기 수득한 박테리오파지 YMC17/07/R4900a_PAE_BP를 부다페스트 조약 하의 국제기탁기관인 한국미생물보존센터(KCCM)에 2021년 2월 26일 기탁하여, 수탁번호 KCCM12962P를 부여받았다.
2-3. 용균성 파지의 용균역가 측정
카바페넴 내성 녹농균들을 각각 맥콘키 한천배지에서 접종하여 배양한 후, 정제된 박테리오파지 YMC17/07/R4900a_PAE_BP를 도말된 각각의 균주에 10 μL로 접종하여 플라그 형성을 확인하고, 역가 범위를 확인하였다.
그 결과, 표 3에 나타난 바와 같이 카바페넴 내성 녹농균 65주 중 46주(70%)를 용균시켜, 본 발명에 따른 박테리오파지 YMC17/07/R4900a_PAE_BP는 상당수의 항생제 내성 녹농균을 용균시키는 것을 확인하였다.
하기 표 3에서 '++', '+' 및 '-' 는 숙주 균주에 대한 플라크 활성을 평가한 것으로, '++' 는 강한 용균, '+'는 용균이 일어난 투명한 플라크를 의미하고, '-'는 용균이 일어나지 않은 것을 의미한다.
[표 3]
실시예 3. 항생제 내성 녹농균에 대한 용균성 박테리오파지의 전자 현미경 분석
상기 실시예 2의 방법에 의해 정제된 박테리오파지 YMC17/07/R4900a_PAE_BP를 감수성 균주 배양 배지(20 mL LB 배지)에 접종 및 배양한 뒤 220 nm 밀리포어 필터로 여과하고, 상층액에 폴리에틸렌글리콜(MW 8,000)을 10%(w/v)의 양으로 첨가한 후 밤새 냉장 보관하였다. 이후 15,000 g의 조건으로 21 시간 동안 원심 분리한뒤, 염화세슘(cesium chloride) 밀도구배원심분리를 진행하여 박테리오파지를 정제하였다. 정제된 박테리오파지를 0.1% 초산우라닐(uranyl acetate)으로 그람 염색을 진행하였고, 투과 전자현미경(Transmission Electron Microscope) 촬영을 통해 상기 박테리오파지의 형태를 분석하였다.
그 결과, 도 1에 나타난 바와 같이, 본 발명에 따른 상기 YMC17/07/R4900a_PAE_BP 박테리오파지를 모양으로 분류하는 기준으로 보았을 때, 육각형 머리에 짧은 꼬리를 가지고 있는 포도비리대(Podoviridae) 과에 속하는 것으로 분류하였다.
실시예 4. 박테리오파지의 흡착능 및 1단 증식 곡선(One-step growth curve) 분석
카바페넴 내성 녹농균을 OD 값이 0.5가 되도록 배양한 뒤, 정제된 박테리오파지 YMC17/07/R4900a_PAE_BP를 MOI 0.0001로 넣고 37 ℃에서 배양하였다. 배양 후 1, 2, 3, 4, 5, 10, 15, 20, 25, 30 분에 1 mL씩 채취하여 200 nm 밀리포어 필터로 여과하였다. 여과액을 SM 완충 용액에 희석한 뒤 플라그 분석을 통해 상기 박테리오파지의 흡착능을 평가하였다.
그 결과, 도 2에 나타난 바와 같이 박테리오파지 YMC17/07/R4900a_PAE_BP의 접종 후 10분 이내에 박테리오파지의 58% 이상이 녹농균에 대하여 흡착하는 것을 확인하였다.
또한, 카바페넴 내성을 갖는 녹농균 균주를 OD 값이 0.5가 되도록 배양한 뒤, 4 ℃에서 15 분 동안 4,000 g로 원심 분리하여 세포를 침전시킨 후, 10 mL의 LB 배지에 희석시키고, 정제된 박테리오파지 YMC17/07/R4900a_PAE_BP를 MOI 0.0001로 넣고 37 ℃에서 5 분 동안 배양하였다. 배양된 혼합 시료를 12,000 g에서 10 분 동안 원심 분리하여 얻어진 펠렛을 10 mL의 LB 배지에 희석시키고 37 ℃에서 배양하였다. 배양 도중 10 분 간격으로 시료를 채취하여 플라그 분석을 통해 상기 박테리오파지의 1단 증식 곡선을 평가하였다.
그 결과, 도 3에 나타난 바와 같이 1단 증식 곡선 결과 약 117 PFU/감염 세포의 높은 버스트 사이즈 (burst size)를 나타내었다.
상기 결과를 통해 본 발명에 따른 YMC17/07/R4900a_PAE_BP 박테리오파지는 카바페넴 내성을 녹농균에 빠른 시간에 흡착할 수 있으면서도 높은 버스트 사이즈를 나타내어 매우 우수한 용균 효과를 나타내는 것을 확인하였다.
실시예 5. 생체 외 항생제 내성 녹농균에 대한 박테리오파지의 용균능 확인
카바페넴 내성 농녹균 (1 X 105 CFU/mL)에 상기 실시예 2에서 정제된 박테리오파지 YMC17/07/R4900a_PAE_BP를 MOI 10, 1, 0,1의 양으로 각각 처리하고 시간별로 OD 값(파장 600 nm)을 측정하였다. 음성 대조군으로는 PBS+SM 버퍼를 처리하였다.
그 결과, 도 4에 나타난 바와 같이 카바페넴 내성 녹농균에 대하여 음성 대조군에 비해 박테리오파지 YMC17/07/R4900a_PAE_BP를 처리한 경우 OD 값이 감소되었으며 숙주인 녹농균 MOI가 증가할수록 OD 값의 증가 속도가 더욱 감소되었다. 즉, 박테리오파지 YMC17/07/R4900a_PAE_BP 처리에 의해 카바페넴 내성 녹농균의 생장 속도가 감소되었으며, 특히 MOI가 증가할수록 생장 속도가 감소하는 것을 확인하였다.
상기와 같이 본 발명에 따른 박테리오파지 YMC17/07/R4900a_PAE_BP가 숙주균 생장 속도를 저해하는 것으로 보아 카바페넴 내성 농녹균에 대하여 용균성을 갖는 것을 알 수 있다.
실시예 6. 정제된 박테리오파지 YMC17/07/R4900a_PAE_BP의 온도 및 pH 안정성 확인
SM 버퍼 40 μL에 정제된 박테리오파지 YMC17/07/R4900a_PAE_BP 1 μL를 넣고, 4 ℃, 40 ℃, 50 ℃, 60 ℃, 70 ℃에서 10 분 간격으로 1 시간 동안 배양한 후 숙주 세포와 함께 플라그 분석을 수행하였다.
또한, pH가 4, 5, 7, 7.5, 8, 9, 10인 SM 버퍼 각각에 정제된 박테리오파지 YMC17/07/R4900a_PAE_BP 1 μL를 넣고 4 ℃에서 30 일 동안 배양한 후 숙주 세포와 함께 플라그 분석을 수행하였다.
그 결과, 도 5에 나타난 바와 같이 박테리오파지 YMC17/07/R4900a_PAE_BP는 4 ℃에서 가장 높은 안정성을 나타내었으며, 50 ℃에서도 70 % 이상의 활성을 유지하는 것을 확인하였다.
또한, 도 6에 나타난 바와 같이 각기 다른 pH에서의 박테리오파지 YMC17/07/R4900a_PAE_BP의 안정성을 확인하였을 때, 첫 7일 동안은 pH 7-10에 비해 pH 4-6에서 높은 안정성을 나타내었으며, pH 7-10에서는 60-80% 활성을 보이며 초반 7일 동안 pH 4-6보다 다소 낮은 파지의 활성을 보였으나 이 활성도가 14일까지 유지 되는 것을 확인하였는 바, 대체로 높은 안정성을 유지하는 것을 확인하였다.
실시예 7. 분리된 박테리오파지 YMC17/07/R4900a_PAE_BP의 전체 게놈 서열 분석
본 발명에 따른 박테리오파지 YMC17/07/R4900a_PAE_BP의 특성을 규명하기 위하여 전체 유전자 서열 분석을 Illumina 시퀀싱 플랫폼을 이용한 전체 게놈 서열 분석 방법을 기초로 분석하였다.
그 결과 표 4 및 도 7에 나타난 바와 같이, 상기 박테리오파지 YMC17/07/R4900a_PAE_BP는 원형의 dsDNA(circular dsDNA)를 포함하며, 88개의 ORF로 구성되어 있다. 88개의 ORF 중 22개의 ORF(ORF 1(서열번호 2), 2(서열번호 3), 3(서열번호 4), 5(서열번호 5), 6(서열번호 6), 8(서열번호 7), 9(서열번호 8), 13(서열번호 9), 14(서열번호 10), 15(서열번호 11), 16(서열번호 12), 19(서열번호 13), 48(서열번호 14), 62(서열번호 15), 64(서열번호 16), 65(서열번호 17), 73(서열번호 18), 79(서열번호 19), 82(서열번호 20), 83(서열번호 21), 86(서열번호 22), 88(서열번호 23))이 기능 단백질이었다. 용균성과 관련된 후보 단백질 중 ORF 9(서열번호 8, lytic enzyme)에서 키티네이즈 도메인(chitinase domain, COG3179; E-value=4.76X10-67)이 확인되었다. 추가로, 박테리오파지의 용원성(lysogeny)와 관련있는 유전자 (cI-repressor, cro-gene), 유전자 재조합 관여 유전자(integrase, recombinase, resolvase), 내독소(endotoxin), 및 단백질 분해효소(protease)와 같은 유전자가 박테리오파지 YMC17/07/R4900a_PAE_BP 전유전체에서 발견되기 않아 인체 적용에 안전할 것으로 판단된다.
[표 4]
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다. 예를 들어, 단일형으로 설명되어 있는 각 구성 요소는 분산되어 실시될 수도 있으며, 마찬가지로 분산된 것으로 설명되어 있는 구성 요소들도 결합된 형태로 실시될 수 있다.
본 발명의 범위는 후술하는 청구범위에 의하여 나타내어지며, 청구범위의 의미 및 범위 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.
<110> MICROBIOTIX CO., LTD.
<120> BACTERIOPHAGE SPECIFIC FOR PSEUDOMONAS RESISTANT TO ANTIBIOTICS
<130> 21PP30872
<160> 23
<170> KoPatentIn 3.0
<210> 1
<211> 63897
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP)
<400> 1
tctgcccgtt ccgcacgcgg tcagccagca cgtcaaggta ctgccgaact gccggatggc 60
ttgcttcctg gccctctagg atgcgatcga cctgctcgaa cccggctacc ggcgcgcggc 120
ggctcgcacg cacaccttcg ggctgcatgc ggttcaactc acgaagcgcg gcgtcacgag 180
attgcatcgt gtcggacagc tgcgcgacgc gctcctgggc gatgggatcg aggtccagca 240
cggtatcggc cagttcttgc cgcgtggcgt cgtcgaggtc cgtacggttc agcagggact 300
ggcgttccag ttcgagctgc tggctgcgca gcgtgtcacg caccagactc tgctcagctt 360
gctggtcaac cggtaggttg ggatcgatgg tgtccggcgc acgcgcagca cgtgcatcga 420
gcctggacgg catactggcc agggcagtgg ttgtgccgct gacggccgcc accggcccgc 480
ccccggcagc accagcagct gcgttttcga ggaacgactg ccgagcttct tcgtcggtga 540
tcgggttcac tccgatctcc gggttgtaga acgactgcgc gccgcggctt accacatcct 600
gcgcgccttc ggtcagtcct tccagcgccg tcgacgtgcc gaactcccgc gcaccgcggc 660
cgatagcacc agcagcgctt tgcgctgcgc cgccggcagc ttcccgaccg agccggccga 720
ggatgcgagc ttcaggcagg atctccagcc cggagctgac cacaccggca ccggtcgagg 780
ccagcgctcg ttcagctggg gtagcagtgg aattcggatc ggtccgcatg gcgtaggagg 840
tttcgccagc ggtcggtgcc aagacagccg cgccgccggc cagcggaccg ccgacagcgg 900
tagcgcccag ggcagcggca ctcaccggtg cggattcacc ggcggcgttg acgacgaatt 960
cccctagggt acgggcgtcg cggatatccc ccagctgctg cgccccggcc tgctgcgact 1020
gcgcctcagc catcttccga tcggcgtagt tgtacaggtt ctgcgcggta gaagacatcc 1080
cagcggattc agccagggtg ccggcgtaat cggcggacag cgcggcagtc tgcgcgttgc 1140
cccggcgcac agccgcgccg gtcaagctcg tagggttgta cgggagattg ggatccgcct 1200
gcaccggtga cgtttccacg tcaccaaggg gccggacggg acgagtttcg tcaaagggcg 1260
tagtggccat ggcggtcctg cgctaagtcg gcggtgagat tccgcctact atagcgcagg 1320
acgccgatta gttggacagg ctgtccaaac gagtgcgcag gtccgggtcc aggccaggga 1380
acgtgcggat ggctgccacg gcgcgctggc ggtcgtccgc gctcatgttc ctcgactgct 1440
ggagcagccg gcgggcatag gcgttggcca gcggagcgaa ttggctggtt cgttcgtcct 1500
gctggcgcga ccggcccagt acgccgggat tgttgctctg gtactggaat ccgcccaggt 1560
tgtacaggtt gccatcccgc gtgcgcagca ccgggtcgcc gttgatgact tggatcgagt 1620
ccacgttcga atccatggtc gggtccagta cgttaccgcc ggccaccact gcgttcggcg 1680
tttcggacag agcgttgcct gctaccgcac cgccgaggcc gccggcggct gcgcccagga 1740
tagcccgccc tgcgctgacc gccctccccg cgggggtacg acgtgcggca gcggtcaaac 1800
cgccgagtgc agcgccaccg aggccaccca ggagcgtacg agggtcggtc tggtcctgct 1860
gcccgcgctg caccgtctgc gctgcgtcga agaaccgctg ctgggtagtc gggtccattt 1920
cgctgaccgg ccgaaggctg gccacggagc catcgctgtt caggcggtac acaccacggc 1980
ggaagttctg gtacgcctgc tgcacagcag cgaggcgttc tcgtgcctgc ggattggtct 2040
gcgattcgct gcgcagcgct tggagctgct gagcgtaatc ggcctcctgc tgctgtaccc 2100
agttcggttg atactgcgac aggaacgctt gggtggcctg cggcactacg gtttcgccag 2160
actccgggtc ttgacggccg aactgggcag ccaaggcggt gttgaagtcc tcccggttcg 2220
tgcctgcgaa gttcgcgtcg tcggccgatg cttgccgccc ctgctgcatg cgcagacgtt 2280
cgaggcccat cagctgctgg aacgcggcgt tctgagcacc gagccgggca cgaagcgcac 2340
ggtcaccgat ctcagcctga cgctcgttgt tgacgaaggt gtccgcggtg ccctggcgga 2400
tggtgcccat ttcgccgaga cgacggttct cacccatcag cgcacgggcc tgcatcaggt 2460
cggcggcact gccgctgcgg atcaagctct ggatctggcc ttcgttgatc cgcatccgct 2520
gctgcgccat ccgagcatcg gcaacagcct gacgacgagc gtcgcgtgca tcgagttcgg 2580
cgatcgacgg cacgccggcg gacgagatcg tgttggccag cgggcgagcg ctcgcagccg 2640
aactcccggt cgtaccggat gcggcaccgg ccccaccggg gatattggtg aacgtcggga 2700
caccaccgac ggtagtgcgc tgcacggtgt cagtaccgcc gccagggcgc gcgaacgaca 2760
ggctggtggg cgtagccgcg ccgagcggtg cgctcggttg gacagcagtc gcctcagtcg 2820
gcgcagcggc agcgggggag ggagtagccg gcgcagcagg cgcagtagcg gcctcggcaa 2880
cgatatctcg ctcggtcact gccggcggag taaccgccgg ggccggggcc gtcactgcac 2940
cggcggtcac cggctcggcg acagtagtac cgcccagcgc gcggaaccga ggggtattac 3000
cctgagcgtc ccgcccggtg atcgggtcta ccgacatgct gctttcgcct ccgggtccgg 3060
tcggcacgtc cccgtctgcg gcggacacca tgacgttctc acgcggggct tgaggtgcca 3120
aaccacgctg ctggaggtct tccagcgggc tgacaccgga ccctccaata gctcggtcaa 3180
gggaacgaac agcgccatca ccggcggcgt accccgcgct gcccagggca gtcgctccag 3240
caataccggt ggcaatggcg ccaggaccag aaggagcgcc acccacaccg ccagcagccg 3300
cgccaagagc acccccaaca ccggcaccca ggagtggggc ggcatcgaag ccaacctggc 3360
gagcagtttg tccaagatcg ccttcggttc cctcgtatac gcggcgagca ttgtcgatag 3420
ccggaatagc accagccaat gcaccgactg cgccgcccaa acgtcggggg gctacgcggg 3480
cctgctgcgc gccgccgagc acgcggttgg acttggccag cgcttcctgc acaccggacg 3540
gcatgggttc cggcggaagc ccacgcatcg gcgcagtgat ggtacgcgtc gcggcgttct 3600
gccggatacg cacagccgag tcgtcagcag cgcttgcggt gggcggcagc ccgctttcac 3660
cgcggcgcag gggccggcgc gttccgtcgc caccggtgta gtcgatctcg tcgacgggaa 3720
tctcttcgac gccgtatccg agcggttgac gagccatgct tcagtcctca gttaaaattc 3780
ttcgcagtat tctatgtcgg tccagaattt acccacaacc ggcggctccg gcgggagcag 3840
cggcacgcgg taaatctggc cattgtcgaa cagcacacac aagccatcct gcactttccc 3900
catgagcggc gagagaatac cggagctggg gaatccagtg tattcctggg tgaaagtcgc 3960
accgataaca gtcgacgaaa ggatgccgtt gttcccgagg acgtaaatca ggtcgtccag 4020
tcctttgacg aatgcaaccg gttgttggtt tgtaggtacg ggcgaagtct gctgccaagt 4080
tccgccgatg cgagcgaagt acgagtcgaa gaaattcgaa ccatcattgg taatgcgcgc 4140
tgatacgata cctacttcac catcgaagta cgccgcgggt gccgggttcg gttgctgcgc 4200
attgacggcg atctcgtaag tgctcgtgtc aataccaagg taaatctgcc cgtcgttagg 4260
atacgccggt ttgcagataa ccagactatc gtagaaatac gtggtggccg gtacgatagg 4320
atactcaaca tgcgtgagta tgctgctacc aacaataccg ccggtaagga ggttaccgcc 4380
attgctggag ttccaagcat tgcgcccagc ccaactcagc gcaccctcct tgttgttata 4440
gaacgtctgg atagtgaagc cttcttggtt accgggtagc atctggatca gttctagatt 4500
gaccagatcc tgcgtacggt agatcgctct gttccacggg ctggattgca tttctaccac 4560
aaaccagtag taccccatgg tgatatcgta gccggcagtg acgaagtttc tgtaaccgct 4620
cggcatcgca acttcggtcc acgacatacc agcatcatcg gagcagaaca ggtaactcac 4680
gtactgccca ccgggcgtgt acccggagct ggtaagcgta agatgcccgt cagtaagcga 4740
cccgtcaatt tgggccaagt cgccagggtt gatcgccggg ggcagccccg tagagttcca 4800
agtcaaaccg gcgtcgttcg agtacaagac gttcaaagag aactgcgtgc gaccgacgag 4860
aaccaacatg cgttggttcc catcggtgac caagttcgag acgaaaccaa ctccgtcgta 4920
tacgagttct ggagtgacag ccattacggg ttacctccac cggccgtagc gctggcgatc 4980
tcggcctgga gcgcagactg ggcgtttgcg gcagcagcgg cggcgtcacc gaacgcgcgc 5040
acagcagtgg ccagggcatc cgccgagttg ttcacgttgg acgcagcgat cacgttccga 5100
tcgttgctga tgccgccttc catgcgagac tcagcggcgc gcagcctgat ctgctcgaac 5160
ccaagctcga cttggtagta gttggccagc gccgaggtca acgagctgta ggccatggct 5220
ttgattcgtc cggcttccaa gtctttattc ggaatgtcga gccactgtcg gtagaaatca 5280
gccagcgcct gcatgatgcc gagtttcaac cggatagcct gctcttccgc gaacttcatc 5340
aggtcgagtt tgatctcttc ggcgcggatg gtttgcgcgc ggttcacgtc agcgatggca 5400
tcggacatgc gctcttcttc acgcgataca gcaccgacca gggcaccggg agggagggag 5460
aatcctcggt tggagaaatc gacacggatc tgctggacag cgctttcacg tgcgcgagtc 5520
tccctgtcgc ggctgatgtg ccattcagct tcgaacaccg acttgtccag gccgaacggc 5580
ttctgtccgg taaggatgcc acacagccac tcttcgggct tggtgcgcag gcaggccgtc 5640
aactccggga aatactgctc aagccacttc tctacctcgc cgtcgaggaa cgccaccgtc 5700
tcaccagtcg tatcaccggg cagcaggtca ccgaagttcg gcggcggctc aatgaccggt 5760
ttctgtagcg tgtagctcag tgacggcttc gaaagcggcg gcgcgaagtt gttctggata 5820
cgggaggtgg tttcccgcgc agtgcgcagg gcatcgttaa ccgtgtcctg caaaaattcg 5880
atcgtatcgt cgatggccat gttcaaatcc cctggatgtc tttgatgcga ggcgcgatca 5940
tcgttccgca gtaccgagca ccagacgctg agccgtagtt ggcgatctta tcccaagtcg 6000
cccccgagtc gtagctgatg taggtgaagc cgtgttcagg tccaggctcc ccggcgaatt 6060
gtgctttccc gccgatggag aacagcaccg tggcgtcaat cagtacctct tcagtgttct 6120
cgtcgacgac ttgcttcact ggcgcgtcca tcagcccagt gtagtaccag tcacgcacgc 6180
cgttcttcaa ttcctcttcg actacgccgg ccagctccaa ggtgttcttg ttcacgtcgt 6240
acacagccat cgccatgttc ccgtcgatga aaccgatgtc ctcgttttcc tggaattccg 6300
aagtcaccgg gaacaggaat ttcccagcgc ctatatgcag gatgttcccg tacatggagt 6360
tacggaacca gttgcacggg cggaacggga ccatctggct gaacggaata ctcacgccgt 6420
ccttggtcgc caccacgatg tcgatactca cgttcggtcc gatgttcccg ttcgggtcat 6480
ggatgaagtc gctactgaaa aacacgcaca cggcattcgt gccgtccgaa tcagctccgt 6540
agatgtactg catgtcgtgc ggtacaccag agaacgtatc gatagttccc ttggtcggcc 6600
cggccaccgt ttcccttcga acgatggtgc cgaactggtt cacccaggcg cagtctacgg 6660
accaatacgg cgtactgatc ccgccattcg gatcgctcgg cggatcggtc tggttgacgc 6720
tgaaggaatc gaacagcacg ctgtcacctg tgtcgagcag cgccaagccg gacgggaaat 6780
gcgagttcgc catgtagcgt tcggaatccc cgttgatgat cttccacgga cggcggtact 6840
gatcagcttc ctgcctggaa tcgatcacgc tgctgccgac gagcagcgcc gtgccatcct 6900
gctggatctg caagctggcg atccacaagc cgcgcgcgcc gtatcgatct tcatcgtcaa 6960
ccatgtcgaa gacagcgtgc gccaccagca gtacacggta aaacaagccg atgtcttcgt 7020
cgttcccatg cccgatcgtg aggccgcggg accacggata ctgcgcgttg ttgaacgtgg 7080
tggccgccgg gctggtaggg tcatacggcg gtgggttcac gcgtttgctg aacggcatca 7140
cgttgttcgc gtcgagcatg atcgagtcag agacacgcat ggaccacggc tgtgtcttcg 7200
gcgcatcctc gccggggtag ttgccgtccg actcgatcca cccagttccc gtttcggcgt 7260
tggcggtgta cgtggcacgc atgaacgacg gcgcaagtac aggcatgtcg tagaagaacg 7320
tgtccgcgcg cgacacaaac gcgaacgggt tcacgtcaaa gacctgcggc atgttcaggt 7380
agttttcgag gtgaatgatc ccgtagtcag gcaacgcgaa cgcgctcggc cgtacaaggc 7440
ttccggtggc gacgctctgc gagaacgtcc ccagctccat cactctgtag ccgcgcgtcc 7500
ccatgtggct aggtagcagc tcctgcacca cgatttgctc cggcggttgc ttcaagggct 7560
tgaggaacga atcccttccg agcgggaggc ggatcagcgg atggtgagtc tgcgcgcggg 7620
acgtgccgtt gtacgggtta ccgcacacca cgacgtaggc ttcggtgtcg agcaccatag 7680
cagtgccgag catgttgctg cgcacgccgc gaacaatata cccgtcgatg atctcgacct 7740
tggtggcgta cttcatgggg aggttgccga gagactgggc cagtttctcg gcgcgcttca 7800
cgaggtatgt gccggagatc gtcaccggct tctttgcaat ggtcaggcgc atcagttcct 7860
ccgatggatt ctgcgggagg aaaccccgac ctccacttcg atgttgtcca gatccgcgaa 7920
cgaagcgtct tcgacttcca ggcgaagcct ccagtggcga gcagcgacgc ctttcgcaac 7980
accatccggc gtgcggaact caggactttc gccggcaagg gtgtacacgc gctcttcacc 8040
gtcatcgccg gtgatgcgga agtacacacg cccgtccgtg gtgataccag cgtacgcgct 8100
cgacaaccgc ttggtgttct tcacgccgta gtcgtcagca ccgaagtcga tcaacgcgcg 8160
gagcagttca ccatcgtccg tctcaccttc gaggcgatac aggccgtcgt tcttgatccc 8220
gaacgtgtca ttacccacgc gggcaaagcc ggtgaagccg aaattctggt aggtggtcag 8280
cgcgccggtc agcacgttga cggcgtactg gagcgcagtc tcccgcgcgg tgctgatgtt 8340
cgagtagacc gccagcccgt cgcgcatcat cagttcgatg gtgctttcca gagtgaacgt 8400
cgtgttcagg ccgaggtagt cgtaggcatc caggctgacc agcatgatca agtcgatggt 8460
gccgctgatc tccatgccgt ccgtgaccat gagcagcacg ggtgcgtcga gcatggcagt 8520
gctgtataca ggcatcggct ccggcaccat cagggtgccc ggcggccaga ggttttccca 8580
aacgtcgatg atgtaccgag acggccactt gccaccggct tctgcgtacg gacgatccga 8640
gatcaaccgc tgcggcgtcg ggatcgtgtt gtccaggcca agcacttcgc cggtgaggat 8700
ggtggtactc ccgaacggtc gagggatatg cgccgagacg taggaccatg gagccacgaa 8760
atcggacgta ccggcttgaa gcaccaagcg cggtagagtc cgcaccaggg tagcgccgga 8820
gtagttcgaa atgttcccca gtggcatggg gacgataccg ttgataacct gcggctcgac 8880
ggcatctgcg atcagtacca tccgcggaag ttcagaatca acaccggcat acgtcgcttc 8940
gtagatggtc gggcgaagac gcgggaccag cgcattgagc tgcgcagacg agttaccgcc 9000
gaacgatggg tcgttcacga agtcgccgac cgagtacagc gtggcgtcag cgtagatcgt 9060
cccgccggaa ggcgtgatgc cattgacgat ggggcgaagc gaagaatcat cgttcgggtt 9120
gacttcgtag aacgtgaccc ggccgccgac gcgcgacatg gcgtaccggt tggtgaaccg 9180
gaagaagtct tcgaagatga tcacaccacg atcgtagata cggaaccggt cagggtagaa 9240
ggcgaacgca tgtgtcgggt ggccgaacga gttgtcgaag cgtccatcag agaacccaac 9300
aaggacgccg gtcggtttat ccggcacggt gaacttcagg atcgcatcac cttcaacagc 9360
cgtcacgctg cggccgccag cgttccatcc ggtcttcgga tcgacgatgg tcttcccagg 9420
gataccgggt tcggacggta cggcaggaac gcagatcgtc acattgacga ccttccacat 9480
cgacgtgtac tgcggaacct tgtcggtgta ctgcggaacg ccaaccgcat acgaaccgga 9540
gccggtggcg ctattggcgt tatgcgatcc gaagtaatca tcgccgatcg gctggccgcc 9600
gtttacgttc gggacgatac gctgctcggt gtagcagtac gccgggcggc cagggacagg 9660
gggccgctca gggaacgtat tcgtttgccc agtttttcgc agcccgttgg ccattacgac 9720
tccggcatgg tcaggtagaa gtattccagc gactgaaccg caccgctggt gaggttaggc 9780
tgagtgatgt tcatgtccgc gccgctcaca gcaacggtgc cctggatgcg cggatcgatg 9840
ttgctcgccg atccatcgtc cgtgggctgt accatgcgga agaacgatgc agtgccagtc 9900
gcaacacagg tgccgttcca gacctcggac agcgatttgg tcaaagtgcc gttgctgacg 9960
gtgctttcga agctcacgcc gttgccggag ccgttcacgc tgatctctac caacagcacg 10020
gccgagccga gcgtagcatc agcggtggcc ggagccgagc cggagtagat tcggattacc 10080
gagccggtca gcaggttgcg aagaggttgg tcggcgatca tcgaattgcg cagaccagag 10140
ctgtacttca gtgccatggt tgtgtcctca cacgatgttg gtcggcacgt acgtgatgcc 10200
ggagataagt tgggcggtct gcccggtggt gagcggtttc ggggatgcga atcgtactac 10260
cgacagaagc agcccgttgt taccgccttt ggtgctcgac gacacgagaa acgcaccgta 10320
cacggtgcgg tcctgcgtta cggtgaactg cgcgcggttg gcgatgttgt ccatggtgcc 10380
tactccgtcg tacgctcggt tccacacggg gcgagtcgtt tcggaatagt tcgtgaactc 10440
ctgcatgttg gtcgggatgt cagcggcagt cgtcgaagac gacgggatgt agttgccggc 10500
gaacagaccg caatagaacg tgctgatcgg cgcggtatcg ccgaacggcg accgaataag 10560
gaaatccaca ccgacctgcg ggatcaggtt gtggacgatc tcttcatcca cgacggtgcc 10620
gtccttgtca cagatcacga gccggtgaat gaatccgtcg aggatcactg cgctactggt 10680
cattgtcgat tacctcaagc tgccagaaat ctccggctcc gagtgaattg gtggtcgttt 10740
ggcctttcag ggtagtgacg accaactggt taccgttgtg ttctagcacg ccggcagcac 10800
catcagtcgc aatgtcggga gcatagttta cccggtttgg cagttcaatg ttcccgctgg 10860
cgtcgcctat ggcttggccg taccgggtaa accaagccgc gcggccatcg ggcagcttga 10920
cagcggtccc gcgcactgcg ccgaagttcg tcttgcgcac cgaactcggc tcgtccgttt 10980
cgacatcggt cagccagtag gtttcctcgt cggtggcgac gaacacgccg gtgtcgacgc 11040
tggcgagcat ggtgatgtcg cgcggtagct ggatgaatcg agtgatgggg ttggtcaagt 11100
gcggccacat cggctcggtc atcacgatga tgttgttgta ggccccaacg atgacagcgt 11160
ggtgcgacac aaggagcgag cacggcggca taggggtcat ttcgtcggta gtgaaccgct 11220
gagtgttatc caccgtggac gtgatgatga acgtgttcag actgaccagc ccctgggcgt 11280
acaacgtcga tccgttcaca gagctgcaat acaccgtgca ggaccgcggg tcgttgcacg 11340
aaatctggat cgctttacca cccggtacgg acacggcaac ggcgtcagca ccggactctt 11400
caccctgctc gccataagct gtcacagcca ccttgtacgt tccggtcggc aagtggccgt 11460
cgacgagact gatggtgtat accggcgacg gcactcccca cttccgaacc gtgttgccgt 11520
cgaaacgaag gctttcggtg ggggtagaca ggtacagctg gttgttgtgt tcgcagccgg 11580
ccacttcacc gttggggtta accgacccga cgacatgccc ctggttggtc ctggcgtcga 11640
atactttgag gtcgccgcca tcgacgaaca gaatggccgt gccgagcggg aacacggccc 11700
ggccagcggc gcagtcattc accttgacga agccggtacg cagctcgaat ttcccaccgt 11760
tggtgggatc catgttcatc gccttgacga cggagttctc cggcagccgc tccggcttgg 11820
cgatgttgtt ggacccgctg gcccagttgt cgcgcgtctc gatgctcatt gcgccagtac 11880
cttcttggcc ttctgccaac ggttttccct gtcctcagct ccattcatcc cgccgtttat 11940
ccggcgggtg atctcgctga accgaccctg gtccgccagg gtattgcagc ccttgtctcg 12000
ccacgtagcg gcggcggctt cgaggccgcc gtcgtaggtg gccatcatgt ccgggtcatc 12060
tacgaacggg cgtccggtca tgacctgtgc cctgcggtag ccatccttgc cggtgacctg 12120
caacgggccg cgaccacgat accgccagcc atcaccactg agcacgtcgc cattgcccat 12180
gcggttggcg tacgtgttgt tggcgatggc ttgcgggttg cgcgcgattt gcgtagccag 12240
ggcgttgggg ccaccgctgt gtgctttgta gcgactgggc cacacagcgg ctaaacgggc 12300
agcgctgtag ttgagatttt cttcgaagcg ggtgaggccg gaggattcat ggccgatttg 12360
agcaaggtac gccgcagcac gcgccgtcga cgtgatgtcg tagcggacca tgctgcgtac 12420
caggggttcg aatacttcgt cgggagcgtc agggaacaac gcctcgaact gctgcttact 12480
gatgaccatc taagacctcc ttcagccatt tctggagttc cacaagacgg tcgcgggaat 12540
ccttggcgat taggttgttg ctggtcgccg tttgaagagc ttccttgtca tctgccgcca 12600
ccatcagctc gaactcggcc ggaactacca tcaggcgctg gtcgggtttc gggaacgggg 12660
cgcactgctg cgtcgaatcc aagggaggcg ttgtagacgc gcacccaatc aggaggaaga 12720
acgcacttac cagcagcggg gttttggaca tagcggacga cctctttaac gacggtttga 12780
gtccgcacct cggtgtcttt ttgttgaaca tccacacggt cggtgctggc cgccgtgatt 12840
ttagcgtctt cgcgcacttt ttgcacagct gctgcccgct gctggtcagc agcttcgcgg 12900
gcctgggcca gcatggcggc tttctcgact tcgcaacggt ccccgcggat cgtccacccg 12960
gctgcgccgc cgaggccggc agcaaccaga aggctgagca ggatcaggaa tggggttggt 13020
tgcataccct caccttgttg ccgatgaagg tgttcaccaa ggaccacatg aacatcgcca 13080
ccagcatgtt gaagccgatc aggatcgaaa gcccgtaccc ggactgcacc agccgggcag 13140
gctgctcgga ccaaatcacg accatggcca ggatcgccag aaggctcatg gcaccgatac 13200
cggccacgag ggtcttatca tcttctcggc acttctcagg gagtcggaaa aactcgacta 13260
cgcgggcgaa cgtgatggcc caaatgagcg acgaaatgat ggtgatgggg agcatcggag 13320
cctcctacgg gaaaacccgt ttgaagaatg ccagcacccg ctctacgacg gtagcttcga 13380
gcgccgtcag gatcgggtag gcaaagaaac cgagcagcat cagcaagctg tctcggtact 13440
cgctgggagg tacgaatccg ccgagcgcct tcgcggcgaa catggcgatg aacacgttcc 13500
ccaggaacaa agagacaacg aacttcttgc ctcggttcag gaacacatgg ctagccgcgc 13560
cgccgaaccc accaagagcc atggcatata gccaatcgct gatgtccgac cagaaccttt 13620
ccatgtctac ccctaatact cgttgtagcg aatcggctgg aacgagcggt ggcttatggc 13680
ctgcgactct ttgatgtcgc cgagttccat gccgaacagc cgaagttgct cattcgattc 13740
cgacttgtcg aacacctcag cgtcttgtac gagcaggccg aggtacttca tgtagaacag 13800
cacggcacgg tcgtaccgag aattgatctc cagcttgtcg ttgatcgtca ggccgcatac 13860
cgggcgacgg tacgcagcga tagtgagctg gagcgcggtg ttgggcttgg ggcggtagag 13920
cgccagttcg acatcgcctt gctggtcgaa ctgcaccgtc aacgtacggt tgctgccgtg 13980
gcagttccaa gcatcttgca cgccgaatgc cgggagctga tcttctacgc agttgatctc 14040
gacttcgccg cgctgggatt cgatccaggc gcggcgagga cggatgatcg cctcgtccat 14100
gatgacgatg ccggtcccag gctccacctc aagggtgaac tggccgacca agcagagggt 14160
tttctcggcg atcttcagct gagcttcccg gatgtagctg accagcagat cgttcgacca 14220
gaagtaaggc tggaccttat cccgcatttc ttcccggaac gtcgtgacaa gatcagctac 14280
acgggtgccc atggcattac tccggcttgt cggtctggta cagcttccag gcggagtcgc 14340
gttcagcggc tttcacttcg aagccggtga tggaggcgat tgcttcggtc ttcggcttac 14400
cgccggaggc gaagtcggca gagtcgccgc gatccaccag agtcttgatg gcggccagga 14460
tctggtcgac gcgttcagcc gcgttgttgt cgatctgctg gtctacggtg gtagcggtgc 14520
ccggctcgcc ggtgagcttc agggaagcgc gcaacttctc gtcggtgatg ctgttcacat 14580
cgacgcaacc agcttcgcgt acagccttca gcacgaggtt gtggttcggg atggaacgcg 14640
gtacgccggc ctcgaaccga aacgcgtgcc cagtgatggt ggccacgacc tgatcggtca 14700
gggagacgta ttggacggtg ttctggacgg gggttttgcc agccatagtg atgtgctcct 14760
acgctgttcg ttgggggatg aaaacagggg agtctttcga ctccccaagc cccgtgaagt 14820
gtatcagttg tacgccgggg agccgtaagt ctcgttgccg cgaccttcga cgatgtaggc 14880
cagcaggaac ttgaacttac cggcggtgcc accagtggaa gcggtagcag tgaaggtgat 14940
cactgcgccg ttcgggtagg tcagcttggc cggagccagg actttcgcgc cggtggtttt 15000
cagatccaga tcggcggcga tgccgtccgg gtcggctgcc agccccggct cgatgacgcc 15060
gatgtccagg gttgcagcac cggcagcgtt cgatgcggtg gtgaccagca gcttgctgat 15120
ctccgggacg aggatcgcgc cgttttgcaa ttcgagggtc agggtagcgg cctgaccgtc 15180
gaccagatcg ctgaaatcga gggtctgctc gatgaacagc gggtactggc gtgcggtgtt 15240
ttccagagtt gccattttcc tatcctccag aggactgggg aacgtggccg cttaggcggc 15300
cacgtacacg ttgatgacac cgaagtcctc ggtgttaccg tcctcgtaga tcgacgggaa 15360
ctgaggcttc aggaagccga ggatcttcgc cacggagata ccgtgcttgt tgtcgtagtc 15420
gaattccttc tcgacccagc gcgggttgcc gatatcggcg aagcccagcg cctgcgcgcc 15480
gcagaagagc atcgagcagc cgtcaacgtt gccggaggca ccccacttgg cacccggagc 15540
catgccgcgg gtgttgtaca cgtggcggaa ctcgtgaatc accagaccat ccacggtcac 15600
gatgccgccc ttgaacagcg ggttcacgtt gccgcgggtg taaccgctac gcaggttggc 15660
gatgtagtcc gggtccagct tcagcttggc catggccagc gggtcgagga acacgtgata 15720
catttcctcg ccgccgtcgc cgcgcagacc acggatgtac ttggtcttcg cgtacgcctt 15780
gaggttgacc agcagagcgt agctcggggt atcagcggcg gtaacgtcgg aggtggcggc 15840
gttcggaacc agcaccttgt tggtgccatc ccagcgcaga cgacggttgg ccgaaggcgg 15900
agtaacgtcg gcggcgaagg tgaggttcgg gaacggcgag ctaccacgca gcgcaccgtt 15960
ggtgcgatag gcatagctca cgccggccag cgacaggaac gccagttggt ccatacggtc 16020
ggccagccag tacgccagca tgtcgcggct ggtagtacgg aagttgacga tggaacgctg 16080
gtcggccatg cgaccttcgt ggacgttggc ggcgcgcatc tggtccagct ggatgacggt 16140
atcgaaggcg gtcagcgcct cttcgttacc ttccagttgg ttgtcgccga ccacaccgtc 16200
gccaaccatg tcagcgatca gggtgattac ggcgcgtgcg cctttctcgt cacgacgcag 16260
ttcggtgatc tgctggatca tcgagttggc atcggtgccg aggaacatgt tgatgaacgc 16320
ggcgttacgc gcttgccgcc agaactgaag ggaccatacg gtcttctgtt cgttggtcag 16380
gcgcgcaaag ttggtgtagt taccttggac gggcaacggc atggctgcat cctcttctgc 16440
ggcatagtgg aaagtggttc agttctgagg tgtaagctgc gcgcttaccg gcggacttgc 16500
ggggaggtgt tgcgtggtcg ctgcgcggac ctggcgaatg cgcaaactat aggcacaaaa 16560
aagcccggtt gcaacaaccg ggctttgtgt tccacgtgga acatcactcc gcgtaatcga 16620
agtcgccgcg tgcttttgcc tgttcagctt cggacatcga ttcgatgtct ttcaacgtct 16680
gcggagtacg cacgagcgcg gaagccgcgg caggcggtgc aacggccggc gacttcggct 16740
ggttcgacac ggcggcggtt gcgcgggata cggcttcttt ccgacgttcc tggcgcgcgc 16800
gatcctgcgg cgtttgctga ccgagcggct tgacagcagc ggcttgttcc acgcccagga 16860
cgtactcgac ggcacgggtc atggcgatga ccttgccgta cttcggcgac agggactgga 16920
acagctcgtt gatctcatca acggtgccct ggtcgaacgc ctcggcgttg ttgtcgtcca 16980
gcacggcgtg agtagaccgc aggttggtca gcagctcttc gaacttcaga ttctccagct 17040
gttcgcgggc acgctcgtca gcgatgctct cggcgcgctt ggtagccatg gcttcctgaa 17100
tcgcgcgcat gtccttgcgg atctgcggca gcagatcgaa gtcgttggct ttcatcgcct 17160
cgatttcgcg cgattccagc ttgtcgtagc tggcctggag atcgaccagt tcagaggtca 17220
gcgcgcggga gcggttctgc tgctccagca ggtgctcggc agcccggcgg cgctcggctt 17280
ccttctgcat gcgggagcgc ggaaccatgt tcgggatcgg tctgcccttg tcatcgagtt 17340
tctgctccgg ctccggttcc tgctccgtcc cggacttgcc ctcgggcttg tcttcgggtt 17400
tgtcttcagg cttgtcttcg ggcttacctt ccggctcgtc tttggctttg gcctcgacag 17460
agttcgggtc cacgggggtg tcaccgcgat cctccgggaa ctcttcttct acggttttcc 17520
gcgcaaagcg cccttgctcg tcacgcgccg gagcgtctgc tttcggcgca gggctgtcgt 17580
cgaacagagc ggcgtcgccg cggtccccac cctcgttgtg cgcgcccgga gtggcgtcac 17640
cggcagggat ggaatcgatg tcgatatcag cctcggcacc gaaggcggca gcaccttcgt 17700
cgatcggggc ggacagtaca tgtcgaagga aattacgcat cagtggattc tccattcttc 17760
gcgggggtag atttcggctc ttgggcggcc ttctctgctt cgatcctcat tttaagccgt 17820
tccgtaaccg cgtccagtcg cagtttctcc cggtcgagtg ctagctcggc agttttgatc 17880
ttgagttcgt tgtctacctt ggtctgttcg agcgccaacc gcgcggcttc gatgtccaca 17940
cgctgctgct cgatgtcggc acgctgctgc tcggtatcgg tgccggcctt gagcgcatcc 18000
gtctcggcct ggacattctt gacgttggcc tgggcggact tgttcgcggc gtcggactgc 18060
gcacgctgcg cctcggcggt gactttcgcc agattcgcct gggcagtagc cagttgcagc 18120
tggcgcagct gctgcgcctc cggcgaattc gcctcgctct gcatctgctc gatgatatcg 18180
gctttgtcca acaggcggct gttctggata agcacggtgt cggggatgtt gatcccttcc 18240
ttgcgcatcg ccagcgcctg atcgaactgg ctgtcctcca gggtttcccg cgcaggcacg 18300
gactggacgg tgacgaggta ttcacccagg gtcaggtcgt tggcgatctc accttccggg 18360
gtcacctcgt tgatggtgaa cgactcgtct ttgttcacgc cgccgccgtt gatgtacagc 18420
agtcgctctt cgtagtagta ggtctgcacg atgctcaaga tcgcacgggc caggaacacg 18480
tcactacggt cgaggttgtc gaggatacga gccatgccgg cgcgcccggc catgcggttg 18540
gtttccagcg cacgggcaga cacgtcctcc cgtgcctcac cgcgcatgta gtcggtcacg 18600
ccggagatcg ccttgatcca tgcctgggct ttctggttca tgccttccaa gccagccggg 18660
agctggttcg gctggatctt gtcgatgtcg ttcacgtcct cgacttcgag caccagacct 18720
gtctcggcac cgcgtgcctg gaggtcgtcg acggtcatgt tcttgagcga cccgtgcttc 18780
accttccagc cgctattggc cgtggtgttg aggatgtgca gctcctggct ggcggttttg 18840
ttcaacagct cctgcacgcc gaacagctgc tcgacgatac cggtggtgtg cccgaagcgg 18900
aaatgcggga agtacggaac gaccgtcagg tactcgtagg gactccatcc gtcgtgcagc 18960
aaggtagagc cagccaccac ggtccaacgg atacgcttgg cgatctgcga aatctgcacg 19020
atggacgggt tccgcatcag gtactcagcg gtcttcagct cgtcccagct gtccggcaca 19080
ggacgcagct ccccggtgcg cgtgtcgacg aacagctccc ggcgggtcag tacgcggtac 19140
tgccggtcga ccacgcggat gtaggcatcc tggcgctggg tgccctcttc ggtcttgttg 19200
atgtactccg gcaacgcgat ccggtcccga tactggtccg ggatgtcatt ggtctgcgca 19260
gaacggtact ggttggccag cgcgcgcagc tcctgggtct tctttttccc gtacagggct 19320
tcgaggctgt tcggagacat ccatcgggag acgatcacgt cttcccaggt cgcggggtcg 19380
tagtcagtcg cgtcggggtc gatcaacacc tctttcgggt tcagggtcgt gacggccacc 19440
tccccataga ggttctccgt gaagtccagg cgcacgtcgt agaacccgcg tccggtgatg 19500
ttcccgtcct cgaacacgtc cgtgcgtttc cacgtcaggt ggttcccctg gctgatgtgc 19560
ttgaacgtct tgttcagggc ggtggcggtt cggtcgtcga cgttcccgta ccgcggactg 19620
aagcggatct cgttccgtcc gccgatctgc tccccgacca tcacgtccat ggtctggagc 19680
accaagttga tcgtcagggc cgggcggcgc tgcgctcgca agcgggtgat atcgtcctct 19740
ttccactggt caccccacca gaagttttgg cacttctcgg cggtgaggat gaacttgtcg 19800
tggccgctgt cgcgcatgta gtcgtatcgg caccacgtcg cgttgaccag taaggactcg 19860
tcgttcttcg acaacgtgcc cggtagcggc aggtcaaagg tgtatgcgga gttgatcatc 19920
gggcgttccc catcatgcgc tcatgtgact gccgttcccg acgccgcgca ggatgtcgga 19980
caactgctgc gcaacggtgc gatccccgcg acgcggccgg cgcgcggaaa gagggagcgg 20040
tgggttctta gtaaggatca gctgtgccat ccatgcaagc gcgtcgacta tatcatcgtg 20100
ccggcctacc gggaatcgaa ggaactcagc cttcatcgtc tcgatccagc gagcgccgcg 20160
gcgcagcgtg accatgtggt tcgccatacg gccctggagc ggccgggcac gtgccgattt 20220
atcggtcagc ggcttcagca gctcaacctt gacgtaaatc ttccgccgct tggcctcggc 20280
ttcgaagtac ggcctgatcg acttccaaat ctgcccatct tccacgccca ggacagggtt 20340
gtgcgacttg taccgctgca cggtgtcgag tatggccgtg accaccttcg agctgtcccc 20400
cgtgcgcata cggatgatgt cgtcgacgtg gatcgtgtcg ttcggcatgt gcaacccggc 20460
ggcgatgacg gtgtagtcac tggtctgctt ctcggtgatc gcgaagtcca cggcgatgta 20520
cgccgtgccg tcgtagcgct cgtccccagg gtcgtgctcg atgaagtagt ccgacttgaa 20580
gtattccccg tcgtccggca ccgggttctg ctggtacagg ctgttccagt cccgtgcgtg 20640
caaaatccgt ttcagattga gcaggtactt ccggctgtac cgggcttcgt gcagagcttc 20700
cccggccttc ctgaacggta cggcgccggg cagcggtgag tcgacgatcg tatcgtcctg 20760
ggtcagccac tcgtcgttct cggccaaggc agcgaagttg acgatcttcc atttctcgta 20820
ctcaggatct tcctgcatcg cggcgcagag ccggccggac aggtcatcat cgtgccagcg 20880
ggtgttgatc agcagcacgc cgccgccggg ggtcaaacga gtcagcgccg tcgaggtgta 20940
ccagtcccaa gtcttctccc ggatcgtctc cgaatccgcc gattcccggt ccttgaacgg 21000
gtcgtcgatg atcagcatgt ggcagcccat accagtcacg ccgacgccaa cgcccgcggc 21060
acgtacaccg ccgcctttcg acgtggccca gtcatcgata cgctcgttga ccagttccaa 21120
gtccgggaag atcgccttgt attcctggct cttcaccgtg ctgaggatgt cgcgggacat 21180
cttctcggcc aagtccatgc cgtagctggc caggatgatc cctgcctccg ggtatttccc 21240
cagcgcccag gccgggaact tccggctggt ctgctcggat ttcccgtgcc gcggcgggaa 21300
cgtgaccatg acgcggggcg accgcccatt catggagtcg tcgagaaatt gctccagtac 21360
gcgcgccagg atctcgtggg cgacggctac ctcgtacttc gagttcatct tctgcacgaa 21420
cgggaggaac cgccggcgca tgagcgtgcg ctcggccatg atcttctgcg cggcggccag 21480
ctggtactcg tggctatccc ggctgacgac cccgatactg ccgtcctcgt agatcacgtg 21540
ggccgaattc gaccgcgtgt tctcgcgcat gatcttcggg ttggcgcggg gcttcttctt 21600
gtcgatccgg tctttcttca acttggccgt tttcgggatc ggcacggtat cgacggtatc 21660
gacgggatca ttcgctacat cgacgatctt gttccctcgg ccggcgacgc ggcaggacag 21720
acagatcccg gtgctgtgcc tgggggtata gatcggcgat tcgcacttcg agcagtgcca 21780
gcgcggctta cgctcactcg acgtattcgg catcttcggc tccttcgatt tcctcggccg 21840
acaagatccg gctgttctct tggatcacct tcaacaactc ggcgtcggtc ttggtctgca 21900
tctgcgctgc gatctgcgct gcgccgccgg tgatctcgat cttgaccttg gcttcgtaca 21960
tcccgtgcat cagacccagt tcccggtagc cggcgatcat cgtgcggggg tcagccatct 22020
gccgggcgat ggcaatggca tcccggaacc cgtggatgat ctcttcgcgc gtgacctcgc 22080
tgatctccat gttcttttcg aacagcgtac gcagcgcgcg ctgtacgccg acacggttca 22140
tcagcttctt ggcatccgcc gcgggggagg ggaagttcgc gccggcggcg gcatcgacag 22200
gactctgccc ctgggccaca cggatgcaga actccctttc catcgggtcg aggtccatca 22260
gggactttgc gcgggtgcgc tggagcttgt agtgacgctg ctcgtcaggg tcgacgaacg 22320
aatgctccga cttgacctca gccactgcgg tcgatgcgcg tgacatggcg gtggccgcct 22380
tggttttcga gggcggccgc cggggagtgg ccttggtagt ggtcgtcttg gtagcggtcg 22440
tcttggtagc ggtcgtcttg gtagcggtct tggtgacctt ggtagcggtc ttggtggtgc 22500
gtgccatgtc gtactccacg gggatgggac ggctgtttca tggcacaaag tgtagcgggg 22560
cagggagtag gtggtccatc cgtggaccgg tcggcatggc tcgcgggttc agtctacgca 22620
gctgccgagg ggcgcgtaaa gaggtcgacg ccgatcagat ttcgagcgat tcgttgattt 22680
tgataagcgc cagctctaca tagcgcaggc ggtcgttcag ggagtcgagt gcattgaaca 22740
aaggactatg tacggcagga gacaccggca cgtcgttatt tgccttgacg gtggtcagca 22800
tgaccggtgc gagccgggcg gccagttcgt ccactgcacg atcgaggcgg ttgacggtac 22860
gctcgatttc gacgatggca tcggccacgg gcgaagaggc cgtagattgc gcagcctgcg 22920
cggtgttgag gtcggcgtga gtaggtgcaa acatggtagt cactcctgta cggggctggt 22980
gaggccgttg ggttccaggc gcacatccat ccaggcgcgg aagccggcca gttcccacag 23040
cttgtcgcgg gcctgatcca gggctttgcc ggtggcgatg cgctcgccga tctcatgatt 23100
gaagttgttc gggtccacgc aggcgctgat ggcagtagcc agggtgaact caccgtcgag 23160
cagcgcgacg gcaactgtcg tggtggtgcc ttctacgacg tggcagcgga caaccacacg 23220
gtcgaacagg ctctggatat acgacgaggg gatgcgcggg gcggtcaaac ccttggcttt 23280
catttcctgc tcggtcttgc tctcggattc gatggacatt cgatcactcc tggggcttgt 23340
tgagttcgtg gtcgtcggtg gtggcgagat cggcgttcgc gccggtgata gcacccgaca 23400
gtgcggacgg ctcggcgtgc atcagctcat gttcggcgcg ttcgatctcg gcgcgcttgg 23460
attcgatcac gtccttgttg ctgtacgaac catgcttgcc ttcttccact tcacgagcca 23520
gctcgtcgat ggagggcagg ccgaaggctt cacgagcgcg ttggatgatg ccgccgtacg 23580
agttgaccag atccatgtgc agggtggcca gttcgcgcat ggcgtcgtcg gcctggaact 23640
ggtcttcgga gtcgatgcac tgctggaggt attcgatacg ggacttgagg tagtcgaggt 23700
cgttgaggtg ggtaacgcag gctgcgatgg tgacttgctt cagggaaggg ttcatgccgt 23760
ggtcctttgc ggttgggttg aacgtggtga atgtagcact gaaacgttca acgtgacaac 23820
cttatgggtt ggtggtttta ttttgaaacc gccatagcaa ctcgacgctt tgcgcagaat 23880
tgccgtagca actcgacgct ttgcgcagaa ttgccgtggg agcggggaga ctggtacacc 23940
cctccccttc aaaacaccca ctccccactt cgggttcgtt ttcgtctccg gccaaaagaa 24000
ttcttacccc ctccccctat gcctctcgtg attcgcggag cgaatcaccc ttactccttg 24060
tgtctttcat ccacactgga gttcgcatca tgaccttgct cgctcgctac aagaccttcg 24120
tttcggttct caaccgtgtg cttgctctca agctcagcct cggcttgatc atcttctgca 24180
tcacctacgt cggcatcagt gcctttggct tctatgcctt gtggttcacc tacggctggt 24240
ggtgcgtacc catcctcgct ggcgctaccg tgatcgtcta ctacacgcag cgcttcttca 24300
tcgacgccat cttcatctga cctaccgtgc gcgctgcgga gcagcgcgct ctctgtctct 24360
acgcattcat tcacttcgag gatctaccat gtccactttc gctgctctga agaacctggg 24420
ttcggccatc gtctccgaca tcgctgccgg cgcacgcgcg accgcggctg caactggctc 24480
ggcctacgag tcggtcagcg ccaaggtcgc gcacaagcgc ggcgagcgcc agatcatcaa 24540
cgagttccgc aacatgctga acgagcatcc tggcgagctg ctggctgcga tgcgcagcat 24600
tcaggatcag ctcgcacagc cggccaagcc tgcacgcaag cctcgcgctc gcaaggcggc 24660
tgcacaatga gccagtcgca ggtcaacgag ttcctggctc tgctccaggc caaccgccag 24720
ctgatggcgc agctgtccga agcattcggc actgcgcttg aaatggccga ccaccacatg 24780
gcgagtgcat cgcggcacat ggctcgcatc aacgacgagc tgctggccgc ggtgcatcgc 24840
atcgagaatc catcgcaggt ctgacgacga gggcgcaccg ggaggtgcgc ccctttttgt 24900
cgttgtggca attccgccac tttatatagg actttgtacc atgacctaca tcaccgatct 24960
gctcgactcc aagtccccgg ctgccgtagc tgctctgcgc accaccgcga acagctgcct 25020
gatgcgtgcc gtcagtcagg cactgcgact agcgcgcatc gagctgcgca acgtcggcaa 25080
tggcatcgac ggcgcgaaca acctgcgtgc caacgccgac gccgccaagg ctcgcgcgaa 25140
gcagctcgaa ggcgctggca agcaggggat caccgctgaa gagatcatcc agcgcaactt 25200
ccgcatgtac tacgcgatcg ctgtacgcct ggaggatcgt gacagcgagt acgagcgcgc 25260
catgaccgtc gaccaagcgt tcgagttggc gaccacgccg cgcgacagca gcaagttgtc 25320
gcagtccgca gagctggctg cactgtcgaa aatctccggc atgtcgcccg aagacatcct 25380
gaagatgcgc gacctcgacg cccgccggtt cgccgactcg gccaaggatg cggtgccgct 25440
ggctcgcacg ctgctcgacg acgtttccca caacggcgtc ggtgaggacg agctgttcct 25500
tgagcttccg gtccagcagc agttccagac cttcgccaag gcaaccgagg ctgcggtcat 25560
ccagctgcaa cgcgacacgc agcgtgctgc tcgcttcctc gaaagtccgg tgcgtgctct 25620
gcgtgacctc gcgttcagcg acgtgaccgt gagcaaggcc gatgcggact ccctggagaa 25680
acagctggag cacttcatcg tcacccacaa gtccgaactg gaattcatgt aaaccctggc 25740
gctcggctct tcggagtcga gcgccttttc cgcgttctac cctcaaccac caaccgcgcc 25800
tgggcgctat ggacatcact atggacatca tcaaaagcag caccaacgaa atcgacaccg 25860
acgccgtgat ggaagaactc cacaacatca tggccagcta cgccgagcgc ggcatattcc 25920
tgtcgctctt cttcaccgcc aacatcgaga tcaccaacaa gaacggcaac gactacgact 25980
tccgtgccgc acgcggcatg gtcagcgtgc cggcctgggt acacggtgga ggcgtcggcg 26040
ccttcatggg cgccatgggt gaaggtccgg agtacaccga caacccgatc accctggtcg 26100
ctcgtgctgc acagcacgct gctgtccatc atgagtacat catcggcgag ctgaacaagg 26160
tcggcgagat tggcctgatc aagcttgtgg ataactccaa gttggacgtg gtgaaagccg 26220
actgatttcc gcacgtgtgt gaggggatcg gagggggccg acccgccccc ttctcccctc 26280
cgccttttct gtatcgatcg ctaacctaag tggttgtttc ttgaaaccaa ttagcttttt 26340
ctatcgctgt aacgatttcg ttccaaacag gatgagactg actctcaaca accgtcacga 26400
tgttacgaaa ttccgtccac cgacgaaaat ttcgtaacac gctccagccc aggcagcact 26460
aggggcacag agctttctgt tacgatgtta cgatcttttc ttctttattc cactacagaa 26520
aataaaaaaa taataataga tatagttaat aagtatatag ggccacatat acactgtatc 26580
tgtagcggaa tagcgcagaa cttcgtaaca ttcgtgacaa aagtggccca aacccgcgtg 26640
gcactaaggc tccagcgtgt tacgaaattt tttgagatcg tgacaatcgt gacaaaattt 26700
cccggccaaa accccgcaaa cccgcgtggc actaaggctc cagcctgtta cgaaattttt 26760
tgaagatcgt gacagaacct ctccgtcact cggcgcaaag ccgcgtggca ctaaggctcc 26820
agactgtcac gaaatttttt ctgtactttg cgtcacacag tgaccaaatc atccatttca 26880
gtcatacaca ggagcctggt atgcccccgt tattcaggat gctggccatc gtcttcatct 26940
tctgcatggc cacctattcc atcggccgct tcatcgacaa ggccgccaag gcccaggacg 27000
agctacagct cgcatgttcg acgcaagggg gtaccttggt agccacccgc cacggaaacc 27060
ccgtatgcgt ccgttctgac gccttcttgc cactccctaa gaattaggag atccagccat 27120
gttcgtcgac gctcttgcct ttggtttcat ggccgccatc ggcatcttca tcctgttatg 27180
gcgtctgcct cgcatcctcg tcctgcatct gctgggtatg ggcttcctgc tcgacacggc 27240
gttcaccacc ctggtgttct ggatgcactg gggcacggcc atcggcatgt tcgtcgccac 27300
gatcggcggc ctgttcgggt ccgccggcat cagtctggcc aaaggcgtgc tcggctcgat 27360
cgacttcaag accaagcagt acaaagctgg ttggttcggt gaccgtcgcc cgcccgagta 27420
caagaccact ccgccggcca actgagcacc cgctcacccg ctcacccgct cacccgctca 27480
cccattcacc cttcccacga ccaaaccctc attgccagga gcacgccatg ccgagctacg 27540
ccgactaccc catgcctacc aagcacagac gcttgttcac caaagtcgag gtatcgaaag 27600
cattcgaagc cgatctggac gaccgcctcc cggaagtgag tgccttggcc atgaccagaa 27660
cctacgcaga ctatggactg cgtggcacgt ccagctatga ctcgtacgtg aacggtttca 27720
tcttcgacaa atccaatgct tccgacgctg ttccgtacat cggctcgaag gctcaactcg 27780
ccaaagccag gacgcgatgc cacggccggt tcgacaagca cgtgttcaac ttggctctgg 27840
tccgtcacat cgccagtcct accactctca cgcagcctcc caggagccag ctcgaccggc 27900
tcatgtgcta cagccagttc accagctgct ttttcgacgg ttgcctcttc cagaacattc 27960
acatggtcga tgcgacgttc acgaattgtg ttttcttcga ttgttcgttc gtcaggtgcg 28020
tcggttaccg tgccaagttc atcaactgca ttttcctcag tacgtttttc cacaaaggca 28080
catgggcgaa cgccaaattc aacggctgca aaatgtacga agtacgcttc cgcctatcga 28140
tagatcccac tcctatgccg gagatacagc tcaactacgt ttccttctac atgtcgaaac 28200
tcgtaggcgt gaccttcgaa ggcgatgtgt tctacgacac cgttttcccg gcgtcctacc 28260
tgatcggcgt agctctgcaa gatgccgatc tgacgaacgt ggatatgcgc accgcgttcc 28320
acgtcgatat caaaagcatg cgcggatgca ggctcagccg acagaatccg acgcagttca 28380
tgtcgatgaa catccacgac tacccgatca tctacacctc gaacgtcata cagatcggtt 28440
gtcaggcgtt cagcatggac cagctgcatt actgcatgag catggacacg caagagctgt 28500
atcagctgtc ttccgatgcg ccggaattgg ccaaaaccca tctgaagtgg ctgctcaaga 28560
ccatcgagcg cttcaaaccc aagccgctcc cgtacgagtg ctgaacgatg aaccctccca 28620
agcgttatcg ccccgatgcg gggttcgagc gccgtgcatg gcgtccccac aactacctgc 28680
tggaccaccc gcggttggaa tggaacccgt acaccaatca gcgcccgtgc agggacttcg 28740
attcgtccca gctggtacag ctccaactgt tcgtcgtggg tcactcacgc gaaatcatta 28800
accgcatcat gtgcgctgca caggagtaac accgtgttga tcgtccacac tcacctcgat 28860
cctcggcaca tgaaccctga acccatcacg ccgccggcac cgttgcccta cgtcagccgg 28920
cgcgcactgg cacgtgtccg tgagtgggtt ccgccgccgg atgtgtgccc gaactgcggc 28980
agcgaagtga agctggtcaa caacatcgag atctaccgca gccgatcgta cggggaatgg 29040
ccctacgcct atcgctgcgt gaacccgcgt tgcgatagct ttgtcgggct gcacaagcac 29100
accgacctgc cgctgggcac gctggccacc aaagccatgc gtgacgcgcg gaaggacgcg 29160
aaagcagtct tccacgacct gatggatcaa tggtccggcg tcttcaaccg ctcggaaatg 29220
tacacctggc tggccaagca gctgggtatc ccgaaagcgc actgccactt cggaatgttc 29280
gatgtcccga cgtgtcgtcg cgcgctgcaa atctgcctcg cagaactgaa ggaacggaac 29340
aaatttggaa aacacacaac cttttgagag caccacccat gagcaattcc aacgacacca 29400
ccagcaccat caccaccatc ctccccgatg atgtcgccgc cgtaaccccc ggctccatcc 29460
cgatgtccta ctaccgcctg ctggccctgc gcgcacagct gcgcatccag gccgctggca 29520
tgaagacccg tagcggctcg atccgcaaga agatcgctgc cgaactcgga ctcaagccga 29580
gggatagcta cgaagtcttc atcgctcgca tcaacgagct gatcgaagaa gccaagctgc 29640
gcgccggaca acgcgctggt gtgctgccca aggattgact ggagaacgta atgctcgaca 29700
agaaacgcga ccgaatcctc gccaaccaga ccccgcatgc gcggaaggtc tacgaatgcg 29760
taccgatagc tgaaccctgg ccggcgcatc agataatggc gcagttgaaa gtcgatcgtg 29820
gttctgcctt gagcgtcgcg gtggttcgtg gctgcttgaa ggctctgcac gaagctgggc 29880
tgatccgccg gccgaccagc gatctgtaca tccgtgagaa ggtgactgaa tcggcggccg 29940
ccacgatcgc cgagccaacc cagccaaccc agccagccca gccagcccag ccagcccagc 30000
cagcccagcc gaaggaaccc agcatgtcca cctcgatcga caccctgctg aaaatcgcac 30060
agcagctttc tgtcctggcc gccgaagtcg aagagaagct gtcggagatc gcctccgaga 30120
tcgagacggc ggccaagcag gtcgagtcca ccaccgcggc cgatcgtgag cagctggcca 30180
agctcaagca gctccagtct ctactgaagg atctgtgacc atgatcaaga ccagaaaaga 30240
gccgcgcagg gatctcgaag agatccgccg caaacacgaa gagtacatcg ccgagcacaa 30300
ggccagcggc ggtgtgaccc aggtctacca gtgcccgttc tgcgcccagc agatcgagac 30360
tgcatcaccg tctaccaagc acaacatgtg ggacaccatg acgagttgcc cctggtgcga 30420
cgggctgcat ttcaagcgcg tgtatttcac gcacgtcgag gtaagagtat gagcacgaac 30480
gaacttccca acccttccat cggcgagaag atgcgcctgc ggcattacta cggctacatg 30540
cgcctgcgct tcaacgctga tggcaccgtc gacgggcaga aaggatcaaa ctgggggttg 30600
ctgctcacca gccgggagtg gatgaagacg cttaccttgt ggcgtcaagg gaggtaagca 30660
tgatcaccac gatctaccac gtgaccgtcg atgtacccgc ttcggtctgg aagcatttcc 30720
acaacgacca gatttatttc tgcgaggtgt gcgaagcgtt caaggggaac gtagggtccg 30780
gcaccaacca ctacgatcag gttgaagaat gggccgactt ccacgattcc tccaccgcca 30840
tcgccgctga ggcaaaagcc aaggcgctga tggcgaaata cgaacgcctc gccaaggtac 30900
ttgaggaaca agctgaagag gggtacgagg gtgaccacta aacctgtccc tcagaagatc 30960
accatcgaag gtgatattgc cacgaacgta cgcaagcgcg gatatcggct cgtgcgccgt 31020
ttcggttcca taccgactcc cggcgacgaa ggcttgtcat ccaccgccat gtggccggtg 31080
ctgctctggc aacacgctgt ctacccggat cggttcgctg tgtcgtacgg cgctgaactg 31140
acctattgcc tggactgggt acaggctgcc gaacgtctcg gtgctgccct gctccacgcc 31200
acaactgtcg acgggaaaat caacgatgac tagcagcaga caactcaagt tcggttcgta 31260
catttccggc accatgcgta cgcaggatct ggtaccgaag ttcttcgaga tcctgatgtc 31320
ggtatcgatg aacgccgcgt accagatcgt gctgaccaga gcgttcgagg acgacatttc 31380
gctatccgat cattggctct tcaaagctat cacggacgaa gagtggccgc atgacgacca 31440
cggttggtgg ctctctgttg aagccgcgga aatggtcgat acgctggtcg atgcgcttca 31500
gaaattcgtg ccggtaggtc attacttcgg cgcgcacccc ggcgacggtt cggacttcgg 31560
ttgctggcgc ttcgaggact cgcatctgtt caccgtgttc gtacgccaga gtaacaacga 31620
aggcaccacg tacgtcgagt cggtgtggac gagtaacgcc accgaagccg ccgagataat 31680
cctcgccaac tgcgccggtg agtggaagtg cctcacgtcg gaactgcgcg tgctgggcat 31740
catcgccagt gaagcagaaa tcgaaatcgt tgagtggaac gacgaggaat agaccgtgga 31800
cgacatccaa gttcggctag ccaagtacaa agaccgtaaa gaagaatctc gatacttcaa 31860
aaccctcttt tacaactacg gcctcagctt tggacacccg aatggcggac gtactcccga 31920
ccgcggtgag ttcacgacct gggtcgaacc ctcgcttcga ttcgtaggta acgcggatag 31980
cttggcgcgc atcgggcacc gaggctggta catcgatctg tcccagcgcg atgttgcata 32040
tgggcaggtc tatcgactct cggccaggaa tggtgaagaa cgcttcctgg ctgcctacgt 32100
ctacagctac gacaccgact gcgtgacgtt cgacatcact gaggtgttcg acgacaaacg 32160
agaagcagcc ctggccgccg atgaaatggc cagaatcgcc gccgagcata gccgcgaagc 32220
tgatcaggaa gacgagatca accagcagaa agaagaagca cgtgagcgcc gcagtgcttt 32280
gcgtgtgcgc atgcgcagca tcatggctgc tctgcggtgg aaacgtcgca tggcgcgcac 32340
ctcgccgccc gtgtacatcc cggacatctt caacaccctg gccgaagaag aactccgacg 32400
ctcgatagct gagcgagcag agctgtacaa gatatggaaa tacggcccgg aggattcgta 32460
atgggaagga aacacctcac cgaattccgc cgcgacgaca tcgccaagtt cgtaattttt 32520
gcgcgcacgt acaacaagtt cgtcgtgatg tacctgcgcc aagggcggaa acacctggcc 32580
atggaagagc gccgtatgcg tcgcgcctcc atggcacagg cgcgccgtat caaggagcag 32640
ctggagggct aggaaatgag tgactgcttc gatcacatga tggatgcgta cgacttcgaa 32700
tcacgtggtt tcgatggata tagctccggg ttcagtcgtg gtcgtagtcg tagatcgaag 32760
acaccgttct cttacgaccc gctgtactac cacaccagta tgcctttcct tcggatcgtc 32820
aaacgaaccg agagagcgat tctgttcgag ttcgacaaac tcggcgagca gtgggtacca 32880
gaaaaacttt gccgtcagtt agacgaagca aacggtaccg tcttcatcta cacgccgttc 32940
attaaatcca tgctgaaaaa caggaaacca taatgcacga cttcatcatc aacctgaacc 33000
tggcttctct cggtcgtcaa ctctcgtcga cttgcggtac gcagaaaggg tacgcgaatc 33060
agctcatggg tcttcttcgc atcgcggatc tcaacgaagt gaagagtatg gagtctgcga 33120
acatccgcat gaccgctgaa caattcgccg atttcatcta tctccgtgca gccgccggtg 33180
ccacgaacgg catcaaagat ttgcaagcac ggcgcgtgcc ggctggccac tctaccaaca 33240
tctccctggc gcgggatttg actcctaccg gtttggatgc acgcaccaac acctaccaac 33300
aaggacgaca tgactccatt ggtagtgacg ctgtatccgt agttgcagac atcaacatgt 33360
ccgccaccgc cggtgcgtta gcgtcgcttg ccgggggtat gagccggttc gcggcagaga 33420
tcgatacgct gcgtgccctg gcctcgaagg tagaagattc gcagttcgtt tcgatctgcg 33480
ggggcatcga ggtcgaccgt gttagcgcgc tcgatctgat gtacggcgaa atccacaaac 33540
gtgagcaagc gatcgccagc atgttcactt ccaaccgtca acagtaagga tcatcaccat 33600
gggtagccac gttgcaatgg cgcattacct cgaccccatt acgggcgaaa agcacaacga 33660
gcacatcctg ctcgacacgc aattgaaaga taggctgccg gatcatccgg tagctatcgg 33720
cttcgagctg aacgacgaac acaagaagtt gcatgctgac ggctacatcg ccctggtcgc 33780
catcgaccgt gcgaaatccc tcggcaccag accgcaggat gtgtatcgcc tgggcacgca 33840
catgcacgtt cgccgtgaag cactcaagca catcctgaac atcaacgacg cggatctggc 33900
actgccgctg atttgggtcg atgtggaagt catcgacacc atcaaggcaa tggctggtat 33960
cgaagaggaa aataccagtg cagaagaagc cgagtaagga cgcagcactg aatgtgctgg 34020
aattcatcgc caacgaagcc ctcgcagcga tcgccaagtt cgaagcagtg cagagcgacg 34080
acaacatgtc ggaactcttc gctacccgga cacgcttgaa ggtgcagctc gacgagctga 34140
gggcagcacg cggcgaatca ctcaccaacg atctgtacct caacgggtcg ttgcgtgacg 34200
tgaagtcgcc ggagctgctg atgctcaagc gcggcgagat cgagtccatc gagtacatca 34260
agcgccgggc gacgatccta cgcaagaagc tcggtatctc ccactacaac gcactggagt 34320
tcctggcgcg cgaagctggt ttcgattcgt accgccatgc actccgagaa ctggagtatg 34380
gcaagtgacc accccgttca atgaaggttt tgtcgttatc gaacacgaac ccgacgagac 34440
gaaaggcgaa ctcgcggagt acctatacgc tcccgcgacg tacgacttcg ctctgcccgt 34500
agagtgggtc aagcgcgccg aagctatcac cggtcagcag gtagtaccgc acttcgtgtg 34560
gttgtacctg ccgaacgatg tagctggcat gcctgcgcca ctcaccctca ccggcgtgca 34620
tatcctgatg cagttagcgc gctacccgta aaccgttcac ccactcgacc actcaactat 34680
tcatttctct acacaaggaa catcggatat gtcgaacaac gccaccgtca agaaagccgt 34740
caagtcgctc agcgagatcc ccgagcagca ccatgtcgcc gagatcgtcc accacggcga 34800
caagctgacc ctgcccgaag gcatgggcgt cagcgatgct atcgagctgc tggagcgccg 34860
ccgcagctac ctcgaagaag ctgtcggcct gacgcgcacc ttcaacgtct tcccctggga 34920
cggcgcgaac gccatcaaca tcgccctggc gcgtcgtttc ggctgggccg ccgccgaggc 34980
tactcctggc ttcttcggca gcactccgcc gaagatgatc accatcgaag tcggccctgg 35040
ccagacccgt cgtgtaccgt ggggtcgctt cagcatgccg ggtatcgaag gcttcgtgca 35100
gaccagcgcc agcatgaaag acggccgtct gtgtttccag ctggtcgcgc aggttctgcg 35160
taaggacgag cagaccatcg agaagctgtt cgatgaagtc gaagacgtgc tgaagcacga 35220
gtcgatctac gccggtaagg cgatcaagat ccgcttccgt gacgacgacg gcaacaccct 35280
ggaaatgccc gagccgaagt tcctcgacgt gagcggcgtg tcgcgcgaca tgctggtgta 35340
ctcgaaagaa gtcaccgact ccatcgaaac caacctgttc acgcccatcg agcgcgtcca 35400
cgactgcatc aagaacggta tcccggtcaa gcgcggcgtc ctgctgggcg gtccgtacgg 35460
caccggtaag accctggccg ccaccgttgc atcgcgtctc gctgtcgacg ccggcgtaac 35520
ctacctgtac gtgccgcgtg cggacgaact ggccgacgcc atcgagttcg ccaagcagta 35580
ccaagacgtg gcctgcgtga tcttctgcga ggacatcgat cgctgcatga gcggcgagcg 35640
ttcggtggcg atggacgaca tcctgaacat cctcgacggc atcgacacca agtcgtcgcg 35700
gatcatcacc gtcctcacca ccaaccacct gaccgacatc aacccggcca tgctgcgccc 35760
cggccgcctg gacgcgatca tcgacgtggt tccgccggat gcggaagctg tcgttcgcct 35820
gatcaagctc tacggcgctg gtgacatcga cgagcaggct gatctgaccc cggcggccga 35880
gctgctggcc ggtgcgattc cggcggtcat cgccgaggta gtcaagcgtt cgaagctggc 35940
ccagctccag ctgcaagcgc cgggcaccgc gatcgagaag atcaccggcg acgcgatcct 36000
gctggcggcg caggccatcc agagccaagt caagctgctg gccgagcagt caatgccgcg 36060
tgtggctccg ctcaccatgg acagcctgct gcgcaacatc gtcaaggacg agttcgaagc 36120
gctcgcaacc gaactggaca gcattcgcca actgtccgaa agcatccgcg aacgcgtaag 36180
ctaaccgttc gtgccatcga aagcggctcc ttcggggggc cgctttttta tcgaggttca 36240
catgacccta tcgttcgatt attccggttt gctgtacttc gctgtcggtg tgctgttcgg 36300
catcctgatc gccccggcag ctatgtcgct gctcaaaccc cgcaacaagt tcatggaagg 36360
tttcaagcat gcggccgtga tcatcgtggg tgccgatgat ccggcggatg caatcctgta 36420
cctgctgaac aaggtcgaag aatcgaagac cttcgatacg tacgaccaat acgacggcgg 36480
tgtagaagcg gccgtggaaa tgttcatcga cggtatgaag aacagcgcac acatcgtgga 36540
ttcgtacgag gtacaccgaa gtgacaccta ttaatctcta ccaccgccac acgcactcgt 36600
atgtgtctgg ctggaagtac ctcgacaact acacctacat cggcaacgca ctcgtcaagt 36660
cgcctatgcg caagctgttc gaagacgacg agagcgtgaa gtaccgcggt gtgattgatc 36720
tgccggctgc gcagcgtaag cacatgcgtc gggtgtggaa acgcatcggt aaaccggtga 36780
gcttcggccg tttcgtactc aatgcgctcg aagattactg ggccggcagt tgccagtgcg 36840
aacacgactg ctgcgggtgt ttctcctacg tggccatagc caagcgcgtg aaccacaaga 36900
agtacaccgt gatcgttcaa ggccggcgca acatatgacc atcgagatca tctaccactt 36960
cttcgactac ctgccctggt acacagcgcc ggtgtggctg cttccgctcc tggccttggc 37020
acgataagga atcgacatgc ctgaattcat catcaccatg ctgatctgca cttcgcctga 37080
tatctgcatt ccgttcaaag acgacagcat gcgctttacc caggaacggt gcgaagaagt 37140
acggcaagag atcactcgcc gttacccgcc cgacaagttc gcattgcgcg tgaagtgcga 37200
agttgtggag ccggtgacca agccggtaca aaccagtctt gtcttctgag gtcaccatgg 37260
aagagaacga aaaacccgcc gccaaaatcg cgcacgccaa gcgtgccgtc cacttcacgc 37320
tcaacgagca caccatcacc aagggcatcg agatagcgaa agatgccctg gccatgcgca 37380
ccggtttggc atccggccag aacgaaaagt acaagttcga cgtggatacc acgatgaacg 37440
gatgggtgct cgtaaccgtc accaaaactg aacccgacga agcatggggt aagtggcgaa 37500
cgctggcgct ttcgccgaca gccctggtcg agttggctat cgccaccggc ttgatcaacg 37560
ccgacctcaa cgtcgaagac ccgctgcata tcgttgcagt cgcgggcgat taaccaacta 37620
catcggaggc cggcatgatc atcgcgtctt tcatggattt aacgctggac gttcacatcc 37680
gcgtggaatg ccggcgtgta actgtgaccc tggtcgagta caagctcgtg tacgtgaaga 37740
tcacgaccgg agaactcgta ctctgccagc ctttcttcga acgccccgcg gtcgaaagtc 37800
acttccgtga gatcgtagaa gacctgatcc ttaaacaacg aggcactgtg caatgaaaaa 37860
gaactggagt tcgatggggc tgaatttcat gcggtcgttg gccgctggtg tgttctctgg 37920
cagcatcggg cgaactgccc accgcacgaa ttacacccct gcggcagtcg ataagcagac 37980
gcccgagcaa atcgaggccg ccaagcagcg cgcgcaagaa cgccgtgaac ggcggatgaa 38040
acgtccgcaa gggttcggag gctgaccatg aacatcaagc atctggcgag catcgcccgt 38100
accaactaca cgaccatttc ggtcgagttc cccgagacgc gcggcaagtt ctacacctac 38160
aaggccgagc tgccgttccc gtcgaccgtc agcatggtcg tggtttcgtc gccctcgaaa 38220
ggctactgct tggcgcgggt cgtggaagtc cacgacgtgc cgcagatcga cgtgaacgcg 38280
tcgtacgact acaagtggat cgtggccaag gtagacgatt cgcgctacat gaccctggtc 38340
gaagaagaca aggaattcac caagcgcatg cgggcgcacg agcagaccaa gatttacaac 38400
gaactgctgg cgcagttccc gcaggccatg gagatcatgg gcagcatcac cggtcgtgtg 38460
cacttggaca agcagcaagc ggaagctctt tcgggagatc cgcacgagca ttggtgatct 38520
atcgctgcac cataccccga tagcgcaagg ctatcggggt acaccagata ttgtgtcaag 38580
ttcattgcat ttgaccgatg ggtaggggca agcccatcct tcacttcccc ctacccattt 38640
tctcgcctgg attagcctat ggacatcgct ttcctgtccg cacccgtgcc tctgacgaaa 38700
acgtacaagc agcttcgcgg acgcatcgaa aaatcgaact acccgaacac ctcgtccttc 38760
acctcctaca ccgaaacacc gaaacgcctc gaagattttt acgccgccat cgtcgagcac 38820
gccaagcaag gccactgctt gctcaagggg cagctcaatc gcaacctcgt cgaggaatcc 38880
cgcgccggct cgaccgagag caaccaagcc accgaatggg tctgcctgga tatcgatggc 38940
ctggaagtcg aatccccgca ggcattcatg gacgccatcg gcctgggcag cgtcagttac 39000
atcgtccagt acagctcaag ctatggggtg cttgacgacc tgctgcgctg ccacatcttc 39060
tgcctgctgg acaagccggt cgctgcaccg ctgctcaagc aatggctgat cgacgtgaac 39120
ttcaacaccg agctgctgtg cagccagatg tccctcacgc cgagcggcaa cggcctgcac 39180
tggcccctgg atatcaccac ctgccagaac gataagctgc tgtacatagc cccgccgaac 39240
ctgatcggtg tacctgatcc cttgcagcct gacgagcgct accagctcgt gaagaacaag 39300
ggtacgcact tcaagctgcc gaagcagatc ggcaccgtca gtgcgaaccg gtcgcggatt 39360
gacgacaagg tgaacgagct gcgcctggaa gctggtatgc ccaagcgtaa ggcgtcgaag 39420
tacaacagca tcggccccgt cgagttcgta gcgaacccgg atcaatgcac cgtcaccggg 39480
atcaaggaag accgtggttt cgtctacctg aacctgaacg gcggcgacag ctggggttat 39540
taccacccgg tcgacaagcc ggacttcatc tacaacttca agggtgagcc gacctacaag 39600
accaaggatc tggtcccgga ctattggcac gaccagcagc gcaaggtcga agaggccgaa 39660
gagtccggcg aggttgtcac gcatttggcg ttccgcgatt tcaactcggc gaagtattac 39720
aacggctggt acgacccgga cacacgggag ttggtgctca agcaagcagc cagcgagaag 39780
cagctggctg actatatggc cagtcaaggc cgtgcgctga gcgatcgaat tcctatctgg 39840
tccatggagt tcctgccgtc cgaggattgg acgctgaacc gtgattacga tccgccggtg 39900
atcaacacgt tcgtgcagag tccttacctc caggccaagc gtccagctaa agcaccgagt 39960
gtgccgacgc ttatcgcgcg tatcatccac cacgcattgg gcggtgacga agaggtaacg 40020
gaccggttct ataactggct cgccgcagtg atgcagaagc gtgtagctat cggcaccagc 40080
tgggtactca gtggcacgca aggcaccggc aaggggctga tctgcaacaa gatcctccgc 40140
ccgatcctgg gcgataccta tgtccagcag aagcgcatgg acgagttgga cgagaagttc 40200
aacgacttca tggaacagtg catctttctc ttcgtcgatg aagtgcagct gtccgaaatg 40260
cgtaacggcc gggcgctgat gcagcggatc aagaaccaga tcaccgaaga acggatcagc 40320
atccgcggca tgcaccgcgc tgggcagatg atggtgaacc acgtcaactg ggtcttctgc 40380
acgaacatgc ctgacccaat ctacctgacc agtgacgacc gtcgcttcaa catcgcgccg 40440
ttccagccca acaaactgct gatcacctcc gaagagatcg aagcgatcga agacgagctg 40500
caacagttct gcgactacct gatgatgcgt gaagtcgatt tcgacctggc gcgcgcggtt 40560
atcatgaccg agcagcgtga gcgcctgatc aacaccagca gcaccagcat cgaactggct 40620
tgcgacgctg tacgccgcgg tgacctccag ttcttcctcg acgaactgcc gagcgatagc 40680
cagtccttcg tgctgcctga caccatgctc aagttgtccc agtacaagcg tgcgcttcgt 40740
gaagtcatcg aacacgcttc tacgggcggt aaaggtgtag gacgggatgt gctccacacg 40800
ctgctgcgct acgtgctacc ggactgcccc acgtccagcc acaagttcac ttcgctgatc 40860
aagcaccacg gcctgtacgt gcagtccatg cgtatcggta cgcgcaccac gcgcggcatc 40920
gaagtggact gggtggtccc ggaaggtgcc ctcgaccaga tcgatggcgt cgccgataaa 40980
ccggtcaacg acgagatttc tccgaagacc aaagccgaac tgaaaaagca cctgaaaggt 41040
gtagccggag gtaaatcgaa atgagcaaca cctataccac gtacgtcatg cagatgccga 41100
ccgatccgaa agcgcgcagc aaattcatcg gtaagctgaa cgacctcgcc gacaagttcg 41160
gcgttgagtt cgtggccatg tccttgcacg acgagatttc ctgggaagag tacctgcgca 41220
acgcagtcgc agaagaatcg tctatggatc tggaaaccct tcgtaccaaa tgggagaaaa 41280
accaatgacc cgtcgcaccg tcgcgaaacc cgccgtcccg actttcgacg tacccggcta 41340
cgacaagctg cgggccgtac tgcacgcagc ctatcagcag gcttcggtcg gtaaaggtca 41400
cgaacgccac ggcagcgaag cagcgttcga agaacaatcc acgcagatca tcagcggcct 41460
gatgggcacc tctgatggga tgtacttcca agccatgaag aagctcaacg agagccgcgg 41520
catggaacac gaagcgcgca agcgtgaact gctcggcgcg atcgtgtaca tcgccgggat 41580
ctacatcttc gaggaagcgc acaatgccgc ggaacgttcg taatttctgg atcgagttgt 41640
ccgtagacgg caaggcgaca gatgtcgcta ccggccctca aggcaaagac ggcgggttcg 41700
atctgctggt caagcaacgt gaccagggcg gcatcattgt cgccctggcg gtgataggcc 41760
gcgcgaagta tgtcggtgac gagatccacc tcactctgac tgcggacggt gaaggtgtca 41820
gtaccgcagt cgaggaaggc ggtgtcgtcg tcctcaagtg caagaccatt cgataggagg 41880
ctggcatggc caagtatatt caactcacca acaccatgcg tgagcacatc gcttcgatgc 41940
tcatgtgcga ggcagcgaaa ccgaaagcgg cggacctgat cgctcgcgta acggatctca 42000
acgacaagtt ctggcatacg cacgcgaaac gtttagcggc tatgggtatc actcccagta 42060
tctggcccga cctgatcgtg aacggcgtat gcacttctgt gctgaccgcc atcccgtgtt 42120
actacgaaac gaagttaggt cagtaccgta atagccgtgc ggaagatgct tctctcaagg 42180
tatacggagt gtatccgcac agcagcttgc ggacctccca agtacacagc atgctcattc 42240
gtagcctgct gagttctgac gctttcgcgc cgctcaacaa gttcatcact acggactaca 42300
agttgaacta cgacttcaaa ttgaagttcg tagcgtctgc tgcggtgcct cgcatcatca 42360
acatgtccgt taaaaccgtg gaagtcgcgg gtatccacca gcccatgggt gagctgtgcg 42420
ctgacatcaa cgaagtgatc cgtgcagcac tcgacttcca taaacaagcg ctcgaacttc 42480
tgcgtgcgtg ccgcacttcc aagcagttgg aagagctgtt ccccgaagcg atgcggttcc 42540
tgccggcaaa agcccaggag agaaaacaag acctcgcacc tgtcgagctg gccgccaatg 42600
tccgcagcat gctgaacaaa ggcgtcccgc cggtcatcac caagtaaaca ccccgccttg 42660
ccaccgggaa accggtggct tttttgttac gctgtaatgt acaatgcagc agactaatcc 42720
ctggagctac cctcatgcgc tggtcgatca gtaagctgca cgtccgcgaa ggctgtgcat 42780
accgctacaa actgaagtac atcgacaaag ttcccgaacc tgaacgtccc ctcccccctg 42840
gtaagtctga gcacgcgaac gaccgcggct ctcgtgtcca cgagcagaac gaactattcg 42900
ttcgcggtga agtggacaag ctgccggcag aatctgctga cttccaagcc ttgatcgaag 42960
acctgcaaga acgcttccgc gccggcttgg tcatgctgga gcatgactgg tgcttcgacg 43020
aagattggga accctgctcg cccgaagagc gggccgccat cgccatcgtc gacgtggctg 43080
tctggatcgt taaagatcgc tggctcctga tcatcgatta caaaaccggg cgcaagtacg 43140
aaaccaagca catggaccag atgcagctct atgccctggc cgccttcaag aaatggccgt 43200
tcctcgaacg agtcaccacc gaactctggt atctcgatat cgacgagata tcgaccagtc 43260
acttcacccg aaaccatatc ccggctatcc agcgcgcgtt ccataaccgc gtcgggaaga 43320
tggaacggga caccgaattc aaaccggccg cgaatatcta cagctgccgg tactgcccgt 43380
acaaggacgg gatctgtccg cacgcggtag acgaaaaaac gcccgtgaag ggcaacgaat 43440
gggcctctga gtggaagata tgaagaacct gtacgctgaa ctgaagaagc gtttcgacat 43500
cgacgtggca ctctccgaca cagggtttcg ttttgtctac ggagccatcg accagtcgga 43560
tggtgattac cgcgtaggca tggcctcttt caagatgggt ctgcgcccgg acccggtgat 43620
gtacaaccgc taccagtacg acatgctgaa ccgcctcaaa ggctacctcg gtgaccatct 43680
acgtgcggac cgtgccctgg ccgagctgtt ccatgctacc cgcatgcgcg cgaagctgcg 43740
gtcccagccc gcagttgcgt gaaggaggac tcatggcaaa gttcaaaccg atcaaactga 43800
tgccgcacca gaagaagacg ctgaagaagc gcggcgaaac ttcgatcttg ctggatctgt 43860
ccgaaccggg caccgggaag tccgtggcgc atgcgacgca cttcgtgaag catcggcaag 43920
caggcggcgg cgctgggttg atcgtcgcgc cgttgtcgtt gatcgatacg gtatggccac 43980
acgagatcgg cctggtgaac ccggacgtgg atgtgagcgt agcgttcgcc accaaccgag 44040
ccaaggcgtt ccagcctggg cacgacatat atgtcaccaa ctacaacggc ctggagtacc 44100
tgtccgaaaa ccccagcctc atgcggaagt tgggaatcga ttggttcctc ggcgacgagg 44160
ccactgcctt caagaacccg caggccaagc gcacgaaacg ctgccataaa ctggttcgga 44220
acgtcgagtt caaagcgctg ctgtccggtt cgctcggcgc gaagatgatc accgattact 44280
ttgcaccgac gctgatactt gacgatggta aacgcctggg atggcagttc agccgattcc 44340
gcgaagcaac ctgctacccg gtgcaagttg gccggcaagc gcacatgatc caatgggagc 44400
cgcgcgaagg cgcagacttg gccgtggctc agctcttgca ggacatcagc atccgtcacc 44460
tcttcgccac cacggtgaag cagagcatcc gcacgatcga attcaagctg ccgccgaagc 44520
tgcgcaagtt gtacgagcag atggcgcggg agcaagccat gttcctcaag gacaaggtga 44580
tcaccgcggc gaacggtggg gcagccgcgc agaagttgct ccagatcgcc agcggctcga 44640
cctacgacaa ccagaaggcc aacaccctgc tcgacatgca gcggtacgaa cttgtcgccg 44700
atctggccga ggaacgcgaa aagaccctga tcgcgttcca gtggcaccac cagcgtgaag 44760
cgcttgagct gctgctgaaa aagcgtgggc ggaccaccgc atatatcgat ggcaccgtac 44820
cgggcgagaa gcgcaaagct atcgtcgaag cgcacaaacg cggtgagatc gatgacctgc 44880
ttcttcaacc gcaagcggct gcacacggcc ttaccctggt gaatgccagg actacgattt 44940
gggccacgcc gacctacgac tacgagctgt tcgaccagct caaccggcgg acctatcgga 45000
ctggccagag ccaggattgc gaagtcatcg tgatatgcgc cgagaacaca ctcgacgcca 45060
aagccttcga ggtctgcacg accaaaggca agcgcatgat gacgatgttc gagtacatcc 45120
gcgacttcac gtaaggatcg ttgcgatgac gattatggtt ccgcgcatcc atgacgggat 45180
gaaacccgtt acgctgcgcc cgctgaaaaa gttcaaaccg ctggtggtcg acttcgaaac 45240
ctactggggt ccgaagtatt ccctgcgcat gatgtccacc agtgactacg ttcgcggtga 45300
ccagttcaag atccactgcg taggtgccaa gctgggcaac gccaagacgc gcatcttcac 45360
cgacatgaag aagttcgctg cgtggctggc taaggtccag gctgagtacg agatcgagtt 45420
aataggccac aacctgtact tcgacggctt gatcctcagc gagtatttcg gattcgtgcc 45480
ggcggcttac cgctgcacga tgtcgatgtc gaaagggctg ttccgcaaca ccatcgcgca 45540
cggccttgac accgtagcga agctgttcgg cctggccggt aaagtaaagg cccaggccaa 45600
cgtgaacacg ttcggcaaat gggatctcac gcggcacgag ttgagtgacc tcggcgaata 45660
ctgcatcgac gattgcgaag acacctacag aatctaccag gccatgcgtc cgtacatacc 45720
ggacgatgaa atggacatca tccacgacac cgttcgttgt ttctgcgacc cggtgcttcg 45780
cgtgaacgga ccgatgctcg aagaagcgat cgccgaagtc gaagccaagc gtgcggtctt 45840
gtacaagcaa gcgatcgaac tggtgaacac cctcgctccg gggctggtca acgccaagcg 45900
cccgttcgag acggtgctgc gatctgctgt cgatttcccg ctgctgcttg aagcactcgg 45960
cgttgaagtg ccgatgaagc agaacgataa aggcttgtgg ataccagcac tggccaagaa 46020
agacacaggg ttcgtcgagc tgtgcgaaga ccctgatcct ctggtccgtc tcctgtgtga 46080
agcgcgactt cagttcacgt cgaaccagac cgtcacgcgt gcgcagcgcc tgctggacgc 46140
tacccaggac ggagcactgc tgccggtgat gtacggctac tgcggcgcat tgtcgatgcg 46200
ctggacagcc ggcaacaaga tgaacctcca gaaccttcag cgcgggtcgg cacttcgccg 46260
agccatcgaa gcgccgaagg gctggcacat catgaccggg gactcggcgc agatcgaagc 46320
acggattctg gcgtacatag ctgggcagtg ggatctggtc gaagcgttcc gcgtcggcgc 46380
ggacgtgtac tccgaattcg ccatggagat ttacccggat gtcgaggtaa gcaaggaaaa 46440
cccggatacg gaaaccgagc gtcacgtagg taagacttcc atcctcggcc tgggttacgg 46500
catggggttc aggaagttca tcaccacgat ggcgaccagc ttcatccccg tgctgatgga 46560
agtcgaagac gccaagcacg tcgtgaacac gtaccgcacg aagtacccga tgatcccggc 46620
gttgtggaag tacctcgaca gcatcctggc cgatatggct gctggtaaca gcgggttcat 46680
cgagttccag tgcgggcttc gcctggaata cgaacctgac cggatctgga tgccgaatgg 46740
cctgtgcctg cattaccccg aactccgtga agagtacgac gaggacactg ggcggaagaa 46800
cggctacacc tactcgatcg tccgcgggaa gaacgtcagc cggaagaaaa tctacggcgg 46860
gctgctgact gaaaacatcg tccagtgctt ggcgcggatc gtagtgggtg accagatgcg 46920
gctcatggcg aaagcctacc gtgtggtcat gaccacacac gacgaagtgt cgatgctggt 46980
ccgggctacg aagacggcgc tggccaaggc cacgaagttc atggtgaaaa cgatgtccac 47040
tgcaccctgg tgggcacctg acctgccggt ggcgactgaa gtgaaggacg ccccgtacta 47100
ctgcaagtag gagatcgaaa tgagcgtgac tctgtaccaa tccgaactga tgacctgcga 47160
aaatctgaag acgggcagag tcacgtacta catgtcggta tgcaacgcca tgcggcggat 47220
ctcgaaagcc gagtatgacg agcgttaccg aaaagcggac ggcttgtgtt gcttgcacac 47280
cgtgactgac aagcactacc gccgctcttg caggaccgtt atctacgagg ttccgaaatg 47340
aagttcgaca agattgagta cagcgtatgc aacgattgct tgctcttcgt ggcgtacggt 47400
gaaccgccgg agaacggtgc tgacatcgaa gccgcgatgc gccgagagat cggcgaagcg 47460
aagaatgcgt acttcgtgtg cggcgtcgag ccaaccgaag atgaccccga tgggatcggt 47520
gaaaacgaat tcagctggca gtggtgcgaa ctttgcctga gcacgctcgg cggtagtcgc 47580
tacggcgtga cgttgatgat acccctggaa gaaggaaccg aggatggcag cgccgaagag 47640
ccgaactaac cccaactggc tggcactgca agatccgaac gacccttccc tcaacaagaa 47700
ttaccggaga tcggtacgct actacaggca gctgttcctg gcatggccga agtggtgtgc 47760
cgatcatccg gggttcaaga aaatctacga cgaagccgcg cgccgtcgta gtgctggcga 47820
ggacgtgcat gtggatcaca tcgtgccgat ctgttccaag ctggtttgtg gtctgcatgt 47880
tccgtggaac ctacagatca taggcgcagg cccgaacctc aagaagtcca acttgtggtg 47940
gccggaccat ccgttcgaga accagtgtct cttcggtggg tccgatgaac ctgagcagta 48000
cgaacttcgt ctgtaattgt tactttggga gttgcaacat ggcaacgaaa aaacctacaa 48060
tctctttcga ccgcgatgcc gcgatcaagg agttccacaa gctctccaag cagatcactg 48120
acctgaacgc gaaagtcaag gaactgacct cgctcaaggc cagcttggaa gaagagctga 48180
tcgaacacct gaacatggaa caactcggca ccgtgacgtt gaagaacgga atgggagtca 48240
agctgcaaga ctccgtggtg ccgcaagccg aggactggga cgtgttctac aaatggatgt 48300
cccggaccaa gaacttccag atgctcgaac gccgcttgac ggttacggcg taccgggagt 48360
tccgggagaa gggcaaagaa gtccctggcc tgcgcgattt caccaagacc aaggtcggtc 48420
tgatcaaccc gccgaagaag taattcggcg gggcttttcg aagctcacaa agtaagcaaa 48480
gcccacaacg taaccgagag gaaatagcct gatggctacc aaaaaaacca ccgacgcccc 48540
ggctaagccg gccaccaaga agcctgctgc cggcaaagct gtagccacca tcggcaaagg 48600
cagcaaggtg ccggtcgatg ccaaggcgct ccaggcacag ctgctggctc gtaagcagca 48660
ggtgctcgac aagctgggcc gtcccagcac ccccaccatc gccgtgcgca acgacaagtc 48720
cttcgaactg ccggacggaa gtatcgtcca ggcaccggag ttcatccgtg ccgtggtgat 48780
cgacttcgct tccgtcaact cgctgtacga aggcccgtac gatccgaaga acccggaacc 48840
gccgatctgc ttcgccgctg gactcggcag cccggattcc ctgatcgcct cggacaagtc 48900
cccgcagaaa caagcggacg actgcgccac ctgcccgctg aaccagtggg gcagcggcag 48960
cggcgatggc aaggcttgca agaacacccg caagctggcc gtcgtactca tggacgagct 49020
ggacgacgag aaccgcgaag gggatcttca gttctacccg ctgaacgtgt cgccgaccgg 49080
tatcaagcac tgggatggat acgtgcgcaa tctggcaacc cgcaacgatc tgctgcctgt 49140
ccaagtcgta accaagatcg gcttcgacgc gcaatcgacc tgggccagcc tgcggttcgc 49200
gccggatgaa gtcctcggcg atgaccaact ggcgcaagtt ctcggtctgc aagaagccgt 49260
tgaagacatg ctgacggccg agcctgattg ggctgggttc gaagcgcagc gtgctgagcg 49320
tcaagccaat cgcaagcctg ccggcggccg ccgcccggct gcgaaaccgg ctggtcgcgc 49380
ccggcgctaa accaaggagg taacgaatga gcaccacgct ggcgagtgcc ctgcgaacga 49440
tccgacagct gtaccgtgaa ctgccgacgt ttaacgccga gcagatagag cgacttgtcg 49500
atctggagtt aaagggcgcg aatcggcgct cggtgctcaa tcgtctcgtc tcccgcgcag 49560
cacagctcgc tgcggacaac aaactgatcc aactccaatc gaaaatcgaa agcaaaagga 49620
accacgagca tggcacgtca acccgccaac aaaaccccga aagtatcgac cctgagcagc 49680
aacccgattc ccgccgacgc caagccggta aaaggaaccg tggtagcgcg cgaaaagccc 49740
agcgttaagc cggctgccgc ggcggccaag gctgctccca gcaaggccga gatcaaggcc 49800
aaggaaaagc gcgtagccga gctgcgtaaa ctggccatcc agacgcagaa ggattacgac 49860
gccgaggtca agcgcatccg cgccgaacgc gacaagaagc aggatgacgc cgccaagcct 49920
gtcgcgctgc tggacaagga aatggaaaag ctcagcgctg agttcaacaa ggcgaaggac 49980
aagctgacca agcagcgcac caaggcgctc gcagcttccg agaaggtcaa ggccaaggcg 50040
cgcaaggaag gtgattcggc gctggccaag ctgaccaagg ccaaggaagc cgacgacaag 50100
aagctggctt ccgacctgtc caaggccgag aaggaactcg ccgccctggc taccagctaa 50160
gccagcacgc accatcaggc cgcctccggg cggccttttt tacctctgga gaaaagcatg 50220
gcgaatcccg agaaccaagc aatccagaac ctgcacacga agctgccaag cttcgtccac 50280
cacgaaaaaa tgagcaaccc gtacagcaac ggcacagctg atgtgtggta tgccgcgtgg 50340
ccgtgcgatt tgtgggtcga gtacaaattc ctggcaaagc ccccgcaacg ggcggtgaca 50400
ctcgacctat cggataacca acgtatctgg cttgcggaca agtaccgcaa ggggcgcgcg 50460
gtcgccgtgg tgttgctgtt ccctgcaaaa ttcggcgggg tgatctacac gcacttgtcg 50520
tggggcgaac ggaaaatcca gctacctgca ccggatgccg accacatcat caagcgtgaa 50580
ctgatcgccg agttcatcgt tcggagctgt acctgtgccg cctttaattc ctctcttgta 50640
taccggggcg aagatcgctc ggtcgctgta cctgatcgcc gcattttccg cggcgacata 50700
cctcattatt cggagcctac gtgatggcaa agcaaatacc tacggaactg tctatcgacc 50760
tggaaaccct cggaacctcc gtggaatcgg tgatcctttc ggtggcgatg gtgacgagca 50820
ccggcgaaaa gttccacata gcaatcgatc cgtccgagca aatcgccgcc ggccgtaaag 50880
tcgatgcgag cacgatcatg tggtggctcg gccccggcgc tggtgaaccg gcgcgcgggg 50940
caatgaccga actcatggcc aagcggaagt acggcatgga agacgccaag ctcgaaatca 51000
tgtcgttcct cgacggcgta ctgaagaaaa acccgcgcgt gcgcgtgtgg ggtaactccc 51060
cgtcgttcga ctgcgaaatg ctggcgaatt tcctcggctg taaaccgtgg ctcttcttca 51120
acgagcgcga tgttcgtacg gcacgcatgg tggtcgggcg tacccaggcc agtaccggac 51180
acgacgcgct ggccgacgca gaagcgcagc tcgtcgacgc catgcgtttc atcgaagtgg 51240
ccgacaagga ggcgcgcaaa tgaacatcgt ggaactcatt gaagcgatcg gcatggacaa 51300
catcgaagcg cagtccctca acaagtccac gctcaaagcc aataccgtca aagacgaaac 51360
cgtgatcaag ttcgtcacga agtccatgac gccgaccgac ttcgtgctcg gcaccaagat 51420
cgggctgatc ttgtggttcg acgcggacaa gttcaacgcg gccgtcgata aggtagaaag 51480
tgaaaaggcc gcggaaggct aaggtccgct gccggtgccg tgaatgcggc gctcggaaca 51540
ccaagcgcgg cgatctgaag ttcggactcg cacgcgctcg gtgccgggcg tgcggaaaga 51600
tcggcacgct gcgcatcgac aaatgggccg acagaagagg atggctggtc ggtaggttat 51660
gccgctgcaa cggtgtaccg ttcccgcacc gcccagggat ggtcgggtac atcacgtact 51720
gcggcgctga gattttcgtg gagtgcttac atggccaggg gcatcggatc gacgaagcgc 51780
cggcaggaac tgtcgaagcg tgcggcccgg ttgaagaacc agggctttac cctttctgaa 51840
atctcgaccc tcaccggtat accgcgcgac aaggtgcata tgcgcgtgaa gctcggcgag 51900
cgtctactga gcctggagtg aagcatgtgg aattattgcc ctgagtgtgg gtgcggaacg 51960
ttcgagaagc acgacagcta caacgtctgt gtgaactgcg ggcaggattg gtatcccgga 52020
acggactaca cgaacgtcgt gcgagcacac ctcagcaaga cgtaccaaga caaggacgcg 52080
gagatcgcgc gctacaagca gctgtaccac aaagcgctcg gtgcgatgga acggttgaag 52140
accccgacca gacgggacgt tgacgccatg atgtgcgtgc tgtcgtcgct cgtggcggcc 52200
atatccctgc tggagcgcgg cgggaagaaa gcagcggcat cggacaccat gttcaaccag 52260
atgctgctcg actacaaagc tgctgtgacc gtaggacgga aagcactacg gcgtatgcgc 52320
ggcgataatg accaagcgta cgacagcaac gcggaacgct tgaccaggga agcgctcggt 52380
cctggggcag gaataaatcc cgacgcaacg tccgtagacg atctgtttct cgacggtacg 52440
ccgccgaaca aaaaaggtga cctatgatcg aaagcatact caagcaaatc gacctgaccg 52500
ccaagctcgg ccaggacggt agtccgctcc aggccatgaa cgcgctgcgc atcatccggg 52560
agactatcgc caagcatgcc gtggtacatc cgacccgtag cgaaggtgag cgcaagctgt 52620
cggacctcgg taatgagctg cacaaccttt cgtgctctct cgcacacgat aacgaagaat 52680
gggctgaaca gctcagtagc atcgcccgcg aactttggag ttggccgcaa ccctccccga 52740
cgcaggccga gcaacactgg ccgaagttgg aacagccagc caaggtcggc ggcgtccgct 52800
tcagcgctgg cgtatcgtcg cggttggtag tcgaagccgc ccagcggctg tacaaattcg 52860
agtccactcc tgagaaagag gcggagcgca tcgagcggct ccaggcgttt cgcgagcaac 52920
tcgacccgtt caacctcgcc ccgcatgctg aagcgttcaa cgaagcgccc gctgaagcac 52980
tcaagccaga gcaggcagag gcggagcggc cggtagtggt gggctaccgc agcggcacgt 53040
ctggcggcat atacgcggat ggctacggcc tagagaaacc tgaaccgctg atgaccgtcg 53100
cccagcacga ccgcatcgtc ggggcgctgc ggttcgaacg ccagcagatg gaccgcgctt 53160
tcaccgcgtg tatcaacgag cgcgacgccg ccctggccag gatcgcggag ctggagaagc 53220
cagatcctga ctacacagca cccgcagatc gtaggctacg cccgcaaaaa ggaacttgcg 53280
ccactgctcg atccatccca acctgatggt agctacatct acattgggct ggaccatccg 53340
gcatgctggg ctgaagagcc gccttacgaa ttcttgaccc ctttgtacac cggtcctgtg 53400
tctcagaaca gcgcgccgga tgggtacgcg cttgtgccga ttgagccact tctcaacatg 53460
atgagtgaca aggatcacga caccagaata acggctgagc gccaactgct ttccatactc 53520
gccgccgcgc ccggcaactc ggctcagcac agcgtgccgg aggaattcag cttcgagtat 53580
cgccacccca atggagaaag ccatacggta acggtcagtc gggatcaagt gattagtgag 53640
atgtccgatt tcctgttcga agcgctgtgc agcaagttct gcaactgcga gccggtgggc 53700
gagacgaacg ttgtcgagtg ttcctgcgac gagtacgcgg aggaattcaa actgctcgcc 53760
gccgcgcccg gcaaggaagt gccgcaggca tggatcgatg ttcaggcaga gcgccgccgg 53820
caggtcaccg ccgaaggatg gacgccggag cacgacgatg cgcacacctg cgacgagatc 53880
gcggccttcg cgtgcttcta cgcgatgccg ccggcggcac gcgactggga caccagcagc 53940
accggctacg gcgacaccct gggcgaggcc attgtgcctg aaggctggga gccgaagacc 54000
ggtgatcgac gccgagagct ggtcaaggcc ggcggactga tcctggccga gatcgagcgc 54060
ctggatcgag cagccatgcg cagggaagac aatgatggag gtgcagagca atgaacctgt 54120
cctgggactt catgaagtcc atcgctgagc gggaaagcgt gaaagaggta ctgtcggaat 54180
tcctcaagga atcgacgctc aaagtgaacg gcgctgacgc actgctggtg ctgcacatcg 54240
tatcggcgta caccacctgc gacggcagcc acggcgggcc agcatgtggt gaccctgatt 54300
gctgcgccaa tcagaaacct gacgacgcga aaattcgcat gcagttggaa cgcgccgtga 54360
atgcattgcg tacgttgtgt aacgtcgaca cgaaggaaga catcgatgcg atgctgctcg 54420
ctatgcgtgc catgcccggt gacttgaacg accgcatcgc ggtcatagca accttggaac 54480
tactgaagga gctgatggaa tgacgaaaga cgaactgatg gaagcggtgc gtggcttcta 54540
cggcgacacg tcgcggtcgc gtgaagaaac acgcgaactg ctcgaagaag tgcgtgacga 54600
gatcgatatc ctgatcgagt cgctgtacga ggacgaatag ccgtcctcca gaaacaagaa 54660
acccggccac tggccgggtt ttttcttgca ccgcaaggaa gcgcgatagc aaggctccat 54720
ccgcagtgct cattttacca gaaacccggc catgtgtcgg gtttcttttt gctctgtaca 54780
gagctatggg gtgcggggtt tcactccggc agcggatacc tcgccttgat ttcctcgacc 54840
ttggcgatcc aggcgctgta gtccggttca gttccggcct tgatcgcgtc gaactcggcc 54900
tcggtcttga gcggatcact ttccaggcgg taggcatttg cccgcgcgac ggctgcggca 54960
tcgtattcag cttgccggcg ttcttcagcc tgctgctcag gggtcaccaa tttgctccag 55020
tcgatactca tttcggtaac tccaccgggc catcggcctc gataagcaac ggctcaggga 55080
atctagcggc ttcgctagca tccacgtcaa gcgggtagcg cagagtcaac tccagccggc 55140
cgtttcttcg tactacagga ccgacgaacc attccgactc aatagcctcg gacggcaact 55200
caccaccctc cgggagcggc gtaaaatcga actcctgacc gttcacagtg agtacatcac 55260
cagtcctgct cagcgacagg tgctcgttgc tatcggggag cggtgcatac ggcgacaact 55320
tgatgatcat cagaaccacc tcccgttggc tatcgcagag attgctgtcg cggttccggt 55380
cgccctcgaa gcgatgtcga atatccgcag cgtcacactg gtcgtactag caaccccgcc 55440
gacggttccc cagcctgcgc cagtccccca gcgaaataga ccgacactca ccgtcgggct 55500
accgacaaac gtcgcaggga aagaccaccc acgagtgccg gtaaacaagc tgccgtaagc 55560
ggtatcgacc gcctgatcgg taacgctggc gttgaaccag cagagctgcg taccgtctgc 55620
gagccggatg tattccccgt tcgcgttgct gcctcgctca agaatagagc cgatcggcga 55680
gcctccagac tgagctaccg taccaagaag ctgcgcatcg gacagcacgc gaatccacgg 55740
ctgccaagta ccagatccct tgcgtcggaa atagaagatg ttcgaagtcc gcggtacgaa 55800
cagctgcacc gcagttgctg cgtcgtaggg gtggtggtag agcatagaac caatagggtt 55860
cagcgaatcg atacccggcg gcagattcga ccagggcgac gtaccgatac cgtagaaccc 55920
acattcgtca gggaccgtgt tcgggtcgga gacggcccgg ttgaacgaca tacttttagg 55980
tacgccgccg atatagttca aggcgtttgc ctgcgtactg gcgttgataa tcgcccggcc 56040
tacggcggtg atcggcgttt gcgcccaggt attcgcaccg ttctgatacg gcagcacgtc 56100
cgttccgccg gccagacccg cgaagttgtt cacccgtgcc gtggccaggg ccgcgaacgc 56160
atcggttgcg gtggaagcgc cagtcccgcc gttggtgata ggtacggtgt cgctggcggc 56220
gaactgggac aggttcccgt tgccgccgcc gttgtcgatt accttgaggg ggattgcgtc 56280
agccattggt caccaccggt acgctgagcg agccaccggc ggcgagcgcc accgggagca 56340
tctggttgtt gttcaacgac acgcgaaggg tgccgccggc gcgcatatac accagcacgc 56400
caagaggtac accgagaagc gtatcgccgg ccggcagctc acgaggaaag ccgctgccgt 56460
ggacgagagg tctgcgggca gccatgcgtc acctcacgcc aggacgatcg gctggcggcc 56520
gatctctacg ttgaccacgg tagcgctcac cgcggtgccc agcggctgaa cgatctggcc 56580
ggaaccggta ggcggagtcg ccacgcccag gccgggagtg gtcgcgctga gccacacgtt 56640
accgggggtc atgccagtga cctgggtgtt cgagccttcg aagtacacgg tggcgttcgc 56700
cgcgctggac acggcagcga ggacgaaacc gtgcgccatc ttcgcagtgc cgccagcagc 56760
atcggctttg cgcactttga acgcgccggc atcggcccac acgttcacat agtcgccggc 56820
agccagcgcc tcggacgctt cgatgatcgc ggtgtcggca ccgataccgg acggcagcac 56880
ggagctgtcg agacggccgg tagagtcgag cgccgggata tcgccggcgt tacccgcgcc 56940
ggccgagacg acagtcgcct cgacctcggt ggggaagccg ttctggttgg aaaggtactt 57000
gtctgccatg tcacacctcc agcgtgatcg ccacgccaat gtcgataaat agagtagtag 57060
ggtcgagcgc gaagcctacg atcagcgaga acagcgcgcc agagggaacg gtttgcgtga 57120
gattgccatc ctggccgagg aacacggcac cgggtgtcca cgcccacccg gagtgctgca 57180
cttcaccgag gcgctgcaca tccactgtgc cgccagggga cgccgcattc agcgacagcc 57240
ccagggtgtt tatccgattg atcagcgtcg cgcaatcagc gtacaccact tggttggcgt 57300
cgatcggtgc gaccatgcga tgcccggaca tcggcaccga cgccaccttc tggatgatcg 57360
cgccgccggc cgggccgggt tcacccttgt cgcccttgcg cccaggctgc ccggccagga 57420
cgacgaacgc cgccgagcgc aagtcctgca cctgctgcgc ccccggctgg atcagcacct 57480
cggtgacggc ctgcgcaggc ggcaggacca tggcggtgta ctccagttgc gacgctggcc 57540
gcgccagggg caggacgatc tccatgtcgg ggtcacgcac aagcagcgcc tgagagcgct 57600
ccctggtgac aagcgcctgc ggtgtcgata ccgccacgga caggcactgg ccgacccggc 57660
ggacgactag agcctgacct gcgttcattt cgctacctcg gccgtgacgg tcactcggcc 57720
ggaccccacc gggtagacca cggtgaggtc ggcggggtcg tacagttcga ggtcgtacag 57780
cgccttgttc cagtccaggg tggcggtcac gtcagcaccg atgacgatgc ttatggtgct 57840
ggtcgggatg tcgatcacga cccggccatc agtcgtgctc ccggtcagca gagcatcggc 57900
gtcacccggc gtgcgccgga tggcgaagcg ggcggcgagg ccagtgaggt ccgcgggggt 57960
atagaagacg atggtaccgg ccccgccgaa tgccttgaac ccgatcccgt tcacgtcatt 58020
gagttcgagg ctgtccgggg tcaagacctt ggccaggtag aactgcccag gctgggtatt 58080
cagctcagga ggggatttca cgctctgcac ctcgaacggc cagccatcag acaggccgtg 58140
cccagggacc gtcagcacga ccggggcggt ggccgtagcg cccgtgatgg gcttgtagag 58200
tttgatcggg tcggcccagc ggaaggcgaa ttcgaacgtt ttcccctgga gaatctgcaa 58260
atcgatggtg caagtcatgg tgcgccctcc tgtgagctgc ggaaagtatg ccagccggcc 58320
cggagctgcg ccacgctgca cgttcccgcc gtagggggta gcagagtggc ggttccacaa 58380
ctggagcgca ccacgggcct atttggtgcc ctacagcctg tatcgatacc gttgatggtc 58440
cagagcacta ctattaattg caacgatgtt acgaaatttc cggaacgggc caaaatttcg 58500
taacacgccg cagccttagt gccacggggc ttacagcgat ttctgttacg atgttacgat 58560
tcttactact ttattccact acagaaaaaa taaaataaat atataaagaa tatagatact 58620
tagggccgcc gggggtacag ggtagtatgt acgtgctcca gctccgaaaa gttttttcgt 58680
gacattcgtg acattcgtga cagcctagtg ccacgcggcc tccagctgac ccaggctgtc 58740
acgatgttac gatcttggcc ctgtccgacc tctcttgttg agaacgtttc tcaaaatatc 58800
gattatggtt aaatgcgcca gggcgatatt tccgccctgg aacctatcga tcgatccaat 58860
ctttccacag cgcgttaccc ggaagagcgc tcagcgcggc ccccgtcacg tccccgtcca 58920
tcgtcttttc cccggccttg agcatgtagc tgaaggtcgg accgagggtg aacgccgggc 58980
tttcgatacc atcggtggcg aactggcgca cgccgagcag gccggcgcgt tccacacccc 59040
tccagatcag ttcacccgcg tcctggctct tgtaccagtc gggttcatcg cccgcgccct 59100
ggagcatggc cttgaggaag tcggcggcga tcatgaaggg cacgtacgcg gccagggtca 59160
gcatcggcgc atagttcccg ttccgcatct cgtgcgtggc gcggtcgagg atggtccgct 59220
ggaagctgta ggtgaactgc ttgaggtgcc acacgagcat ccagtgcggg tcactggccc 59280
aggctggacg gtccgccgcg tgcgggcgca ggactgcgcc gtccacccag cggccgatgg 59340
cttcgcgcac cagacggctt ttctcgatgg cgtccttcgg gttcatgccc tgggcgatga 59400
agtcctgcgc acggaacagc aggcgaccgt tcgcgtcggt ctgcacgtcc ttggcggtga 59460
taccaagctc gtcgaggtag cgtgtgctgt gctggttgac gcccgcggcg tggcgaatga 59520
tgaacttctc ggcggcgacg gtggccgccg agcgcatagc cgtgttccaa ccttccatca 59580
ggttgtactt gaacagcagg ttgttggtct tgcgcgccca gtccgacatg tagttggagc 59640
cgtacatgtc acccagcagg tcgagcacga acgactcttc cacggtgccg acatcctcag 59700
cgaagcgctg aatgtcgagc ttgttgccgt tgcgccgcag gctctgcggg atgttccgta 59760
caccggcttt gaaggcggtc caggcatcgc tcacttcccc gccgcgtacg acgatgccca 59820
gcgggtcgat aagggagctg aaaatcgaca gcggcagcac gacgaggttc tgccaagtga 59880
tcaggccgga catggcgctg cgcaggtgcg ggtcgatgtt gctaccgagc gtgccttcga 59940
gcgcacggat agccggcgct acatcccgtt cgatctgctc gtccgtcagg ccgtaccgct 60000
tggcttcttg cagctggtcc ttcaggcgtt caccgttccg tccgaagtgc ttcgtgtact 60060
ccccacgctt cgcagcctgg gtgacgtagc gggtcagcac acggacgata tccgggtcca 60120
tgtactgtgc gacggctgca cgatccttca gtcggatctt ccgttcgttg accgcctgca 60180
tgtacgggga gtagccggcc aagtcttcac tcagcgccag ttgcccctcg gtggtggtca 60240
acgtctcggc cacggaggta gcgatgtcgg gcgtcatgtc gatccagttc ccgttgtcgt 60300
cacgtacttg cccgacctgc accagcgcat cgacgaagtt atcgaagtcg gcgtcgatcg 60360
cctcccgact ccacgcctgc gggaagtagt cctgaacgtt cgccacgtcg acgttggaca 60420
ccttcatgta gttgaagatg cgacggagca acgacttggt gtcgtcgtac ttctgcgcca 60480
tggccggatc ggtcgggcgc acgttcctgt gaagcgccgc ggacagatcc gccagttgct 60540
gctcgtccat ggtcttgatg atgttggcca gctgcgtacc gaacaggttc gtcacttccc 60600
gcacggtctg gatgtacccg gcgcgttggc cctgggtatc gctgcgcgcg tagaactggt 60660
cagcgatctt gctcaacgcc gggttaccgt agttcttcaa ccggccgtgc gcggtgcgca 60720
ggaacttccc ggtgagcgta ctcacgcggt cagccactcg actgcttacc agggcgcgct 60780
ccgggccgga cagggactgc atcaccacgc ggttgacagc gctcggccgg cgcagcttcc 60840
catccttgaa tgcctggagg tacagctcgg ctttctgctc gttgttcagg atcgacaagg 60900
tgccgcgaat ccacccagcg aaccgggaca tccacgtctg cggctgcgcc tggatgtcga 60960
gcatgccact ggcccacaac tcgtacatgt aggcgatgcg ttcctccggg tcgctgagct 61020
gttcgagcgc ggccggttcg ttggccagca gggagcgcat cttgccgagc accaccgggt 61080
tactcgctgc gcggtccagc gccttgatga actggctttg ctgcttctgc ccgcgaagga 61140
cggaaatcaa cgcgtgcatg gattcatgga acgccgtgga catcgggctg gcggcgttga 61200
ccgctacctt gatgaaccgc tgcatggtcg ggttcccgtt gatgtccggg cgggtagggt 61260
ccagtttctc ggtgaacata ccgctgatac ccggcagcct ctcgatgctg aacatgacat 61320
cgctcggcag cacgcgagtg atgtagtcgt tcaggtcttt ggcttgctgc tggctcattt 61380
ggctcgcacc ctgcggccgg gcactctgct gggaagtctc gctgaggtac tgctggtgat 61440
acgcctccag cgcgtcgatg ttatcggaca ggtacgtcac agagcggcca gccagcccgg 61500
cctcgaagaa cgcgtcgtcg gcgatgaacg acaagcgccc caggcgcaga agacgctcag 61560
tcgctgccgg gtcagcccat tgtgccgaca gctgcttgtc gatccctgcg ccgaggatgt 61620
cccgcgcgcg ctgaacaccc tggcgagtgt cgaggctccg gcgggcttcc cggttcgccg 61680
ccgggttcat ggactcccgg cggttgtgca ggtcttcgcg cgtggcacgg tcgaaggcac 61740
gggccagatc accagcgatc tttgcctgcg ccggcacggt gatgtcgagc acgggcacgc 61800
cgatccggcg agccagcatg acggcggggg tactggcacc ggcggtgatc accacatcca 61860
cggggtcggt tccggtcggc cccaagatcc gcgcgtacgc gctcttgctg tacgggccgg 61920
tatcctgatc cacgtcgagt ctggtcccgc tgatggtgaa cccccggcgc gtgtaggcgt 61980
tcatcaggtt cgtggcgtcg cggctgcgaa gcacctcact acggttcaag gcgaaagcga 62040
ccttcaacgg cgtgccgttc atggctgcgg ccatcggcgc ggcccaggca cccggtacgt 62100
tcgtctgcgt ggtgttcatc cacgaccgct gctgcacgct ggcggcgacg ttgttcatgt 62160
gcgcgccgaa gtccagcggg gaaggcccag gccggcggcg gcctatcggc gtcggttcgt 62220
tccgcgcggc cgcaccttcc tgcccggtgg cggcttcgat ggtctgcgcc tgcatgcgct 62280
ccgggtcgag ttcctgcatg ccctgctggg cagcgaaatc ttcgaggttc cggcgttgca 62340
gctgctcgtc ggtgccggtg ttgtccaccg gagcaggccg gcggtcgagt tggcgctgcc 62400
agaagtcgcg cacggacggg tcttgggcct gggcagcgcc ctgggccagc aggcgtaggc 62460
tttcgcgcat tgggccgcgg tcggcaacgg tcctggccag ggtgtcgatg gggctgccgg 62520
gggtgcgcag ggagcctaaa tccatggccg gaggcagtgg ttcgccggtc agggtggcgg 62580
tattaccctc cagagccacg ccacgggggc tggcagcgcg caggagacgc gctgcggctt 62640
cgggaatggt agcggtgccc cctcgccgct gaagcgctcc caggagcgtc tggacggcgt 62700
attcgtcgat caagcgctca acgtccgcct gtcgtgcata ttgcacggtt cgctccgggt 62760
tttcgtacgt ttgtaccaag tcttggagcg cttcggcggt cgggctatcc aggccgatgg 62820
catcacgagg caggccggcg cgcggctggt ctgctccctg gcgcaggtcc gccacggtga 62880
ctgctacctc gccgctcccg tccttgtacc gggccaccac ggcggtgtcc ggtaactgga 62940
actggtagcc ggcgtcggcc agggtgccca ggccatcgga caaagcgtca cgcagcgcct 63000
gggcgtcacg acgaccgaat acctgcgcgc ctaccagacg gcgcaggtcc acggctacgt 63060
tcgtgccctc cggcgtcgtg gcagcgatgt agctgccggc ggacgggttg ttcggctctt 63120
ggttcagccg ctcaacggta gaacgacgaa gctgccgtac gctgcgaagg gcttgtgctg 63180
cacccgtagc gtcgggtcgg actgcccgaa caaggaccga acttgccagg gcgtcaggcg 63240
acagcccaag ttctgctgca acgtctgcgg gatcgacacc gagttcgcgc aaggctcgtt 63300
cagcgggcac gcgctcgata gacccgtccg ggttcgctct tcgagctgct tcttcggcac 63360
gctgaagtcg ttgcgtatcg gcacgggcga ttggggcggg gataccgagg ccgccagttt 63420
gaatccggcg gtttccggtg gtatcgccga accagttctc ggcggcggac tcgacggttc 63480
gagcttggtc gaactccccg ccgtcaagtt catcgtcaag agcgccagca gattggggag 63540
catcggatac ctcgcttgtg ctacggctgg gggactcacc gcgcaggctg gcgtccaggc 63600
cgtcgagcac ctgctgcggg ttggcgaagg cgcgttcgag gaacggttgc agctcgccgg 63660
tgccggtggt gagttcgaca cgcaacgcat tcgacagctg acggagatcc tgcggtcgca 63720
tggtgtcgcg gtactcaggg cgcaggcttt ggagcaggaa ttgatcgaag tcaccacgac 63780
gttgctgatc ttgccggatg gcacgcgcgg cggcttcatt cggttccagt gcgttcagga 63840
ccgagtacgc acgctcaccg aacacatcca gcgcaccgtc gatggtgttc tcgtcaa 63897
<210> 2
<211> 2430
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 1
<400> 2
ttagttggac aggctgtcca aacgagtgcg caggtccggg tccaggccag ggaacgtgcg 60
gatggctgcc acggcgcgct ggcggtcgtc cgcgctcatg ttcctcgact gctggagcag 120
ccggcgggca taggcgttgg ccagcggagc gaattggctg gttcgttcgt cctgctggcg 180
cgaccggccc agtacgccgg gattgttgct ctggtactgg aatccgccca ggttgtacag 240
gttgccatcc cgcgtgcgca gcaccgggtc gccgttgatg acttggatcg agtccacgtt 300
cgaatccatg gtcgggtcca gtacgttacc gccggccacc actgcgttcg gcgtttcgga 360
cagagcgttg cctgctaccg caccgccgag gccgccggcg gctgcgccca ggatagcccg 420
ccctgcgctg accgccctcc ccgcgggggt acgacgtgcg gcagcggtca aaccgccgag 480
tgcagcgcca ccgaggccac ccaggagcgt acgagggtcg gtctggtcct gctgcccgcg 540
ctgcaccgtc tgcgctgcgt cgaagaaccg ctgctgggta gtcgggtcca tttcgctgac 600
cggccgaagg ctggccacgg agccatcgct gttcaggcgg tacacaccac ggcggaagtt 660
ctggtacgcc tgctgcacag cagcgaggcg ttctcgtgcc tgcggattgg tctgcgattc 720
gctgcgcagc gcttggagct gctgagcgta atcggcctcc tgctgctgta cccagttcgg 780
ttgatactgc gacaggaacg cttgggtggc ctgcggcact acggtttcgc cagactccgg 840
gtcttgacgg ccgaactggg cagccaaggc ggtgttgaag tcctcccggt tcgtgcctgc 900
gaagttcgcg tcgtcggccg atgcttgccg cccctgctgc atgcgcagac gttcgaggcc 960
catcagctgc tggaacgcgg cgttctgagc accgagccgg gcacgaagcg cacggtcacc 1020
gatctcagcc tgacgctcgt tgttgacgaa ggtgtccgcg gtgccctggc ggatggtgcc 1080
catttcgccg agacgacggt tctcacccat cagcgcacgg gcctgcatca ggtcggcggc 1140
actgccgctg cggatcaagc tctggatctg gccttcgttg atccgcatcc gctgctgcgc 1200
catccgagca tcggcaacag cctgacgacg agcgtcgcgt gcatcgagtt cggcgatcga 1260
cggcacgccg gcggacgaga tcgtgttggc cagcgggcga gcgctcgcag ccgaactccc 1320
ggtcgtaccg gatgcggcac cggccccacc ggggatattg gtgaacgtcg ggacaccacc 1380
gacggtagtg cgctgcacgg tgtcagtacc gccgccaggg cgcgcgaacg acaggctggt 1440
gggcgtagcc gcgccgagcg gtgcgctcgg ttggacagca gtcgcctcag tcggcgcagc 1500
ggcagcgggg gagggagtag ccggcgcagc aggcgcagta gcggcctcgg caacgatatc 1560
tcgctcggtc actgccggcg gagtaaccgc cggggccggg gccgtcactg caccggcggt 1620
caccggctcg gcgacagtag taccgcccag cgcgcggaac cgaggggtat taccctgagc 1680
gtcccgcccg gtgatcgggt ctaccgacat gctgctttcg cctccgggtc cggtcggcac 1740
gtccccgtct gcggcggaca ccatgacgtt ctcacgcggg gcttgaggtg ccaaaccacg 1800
ctgctggagg tcttccagcg ggctgacacc ggaccctcca atagctcggt caagggaacg 1860
aacagcgcca tcaccggcgg cgtaccccgc gctgcccagg gcagtcgctc cagcaatacc 1920
ggtggcaatg gcgccaggac cagaaggagc gccacccaca ccgccagcag ccgcgccaag 1980
agcaccccca acaccggcac ccaggagtgg ggcggcatcg aagccaacct ggcgagcagt 2040
ttgtccaaga tcgccttcgg ttccctcgta tacgcggcga gcattgtcga tagccggaat 2100
agcaccagcc aatgcaccga ctgcgccgcc caaacgtcgg ggggctacgc gggcctgctg 2160
cgcgccgccg agcacgcggt tggacttggc cagcgcttcc tgcacaccgg acggcatggg 2220
ttccggcgga agcccacgca tcggcgcagt gatggtacgc gtcgcggcgt tctgccggat 2280
acgcacagcc gagtcgtcag cagcgcttgc ggtgggcggc agcccgcttt caccgcggcg 2340
caggggccgg cgcgttccgt cgccaccggt gtagtcgatc tcgtcgacgg gaatctcttc 2400
gacgccgtat ccgagcggtt gacgagccat 2430
<210> 3
<211> 1173
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 2
<400> 3
atggctgtca ctccagaact cgtatacgac ggagttggtt tcgtctcgaa cttggtcacc 60
gatgggaacc aacgcatgtt ggttctcgtc ggtcgcacgc agttctcttt gaacgtcttg 120
tactcgaacg acgccggttt gacttggaac tctacggggc tgcccccggc gatcaaccct 180
ggcgacttgg cccaaattga cgggtcgctt actgacgggc atcttacgct taccagctcc 240
gggtacacgc ccggtgggca gtacgtgagt tacctgttct gctccgatga tgctggtatg 300
tcgtggaccg aagttgcgat gccgagcggt tacagaaact tcgtcactgc cggctacgat 360
atcaccatgg ggtactactg gtttgtggta gaaatgcaat ccagcccgtg gaacagagcg 420
atctaccgta cgcaggatct ggtcaatcta gaactgatcc agatgctacc cggtaaccaa 480
gaaggcttca ctatccagac gttctataac aacaaggagg gtgcgctgag ttgggctggg 540
cgcaatgctt ggaactccag caatggcggt aacctcctta ccggcggtat tgttggtagc 600
agcatactca cgcatgttga gtatcctatc gtaccggcca ccacgtattt ctacgatagt 660
ctggttatct gcaaaccggc gtatcctaac gacgggcaga tttaccttgg tattgacacg 720
agcacttacg agatcgccgt caatgcgcag caaccgaacc cggcacccgc ggcgtacttc 780
gatggtgaag taggtatcgt atcagcgcgc attaccaatg atggttcgaa tttcttcgac 840
tcgtacttcg ctcgcatcgg cggaacttgg cagcagactt cgcccgtacc tacaaaccaa 900
caaccggttg cattcgtcaa aggactggac gacctgattt acgtcctcgg gaacaacggc 960
atcctttcgt cgactgttat cggtgcgact ttcacccagg aatacactgg attccccagc 1020
tccggtattc tctcgccgct catggggaaa gtgcaggatg gcttgtgtgt gctgttcgac 1080
aatggccaga tttaccgcgt gccgctgctc ccgccggagc cgccggttgt gggtaaattc 1140
tggaccgaca tagaatactg cgaagaattt taa 1173
<210> 4
<211> 957
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 3
<400> 4
atggccatcg acgatacgat cgaatttttg caggacacgg ttaacgatgc cctgcgcact 60
gcgcgggaaa ccacctcccg tatccagaac aacttcgcgc cgccgctttc gaagccgtca 120
ctgagctaca cgctacagaa accggtcatt gagccgccgc cgaacttcgg tgacctgctg 180
cccggtgata cgactggtga gacggtggcg ttcctcgacg gcgaggtaga gaagtggctt 240
gagcagtatt tcccggagtt gacggcctgc ctgcgcacca agcccgaaga gtggctgtgt 300
ggcatcctta ccggacagaa gccgttcggc ctggacaagt cggtgttcga agctgaatgg 360
cacatcagcc gcgacaggga gactcgcgca cgtgaaagcg ctgtccagca gatccgtgtc 420
gatttctcca accgaggatt ctccctccct cccggtgccc tggtcggtgc tgtatcgcgt 480
gaagaagagc gcatgtccga tgccatcgct gacgtgaacc gcgcgcaaac catccgcgcc 540
gaagagatca aactcgacct gatgaagttc gcggaagagc aggctatccg gttgaaactc 600
ggcatcatgc aggcgctggc tgatttctac cgacagtggc tcgacattcc gaataaagac 660
ttggaagccg gacgaatcaa agccatggcc tacagctcgt tgacctcggc gctggccaac 720
tactaccaag tcgagcttgg gttcgagcag atcaggctgc gcgccgctga gtctcgcatg 780
gaaggcggca tcagcaacga tcggaacgtg atcgctgcgt ccaacgtgaa caactcggcg 840
gatgccctgg ccactgctgt gcgcgcgttc ggtgacgccg ccgctgctgc cgcaaacgcc 900
cagtctgcgc tccaggccga gatcgccagc gctacggccg gtggaggtaa cccgtaa 957
<210> 5
<211> 1863
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 5
<400> 5
atggccaacg ggctgcgaaa aactgggcaa acgaatacgt tccctgagcg gccccctgtc 60
cctggccgcc cggcgtactg ctacaccgag cagcgtatcg tcccgaacgt aaacggcggc 120
cagccgatcg gcgatgatta cttcggatcg cataacgcca atagcgccac cggctccggt 180
tcgtatgcgg ttggcgttcc gcagtacacc gacaaggttc cgcagtacac gtcgatgtgg 240
aaggtcgtca atgtgacgat ctgcgttcct gccgtaccgt ccgaacccgg tatccctggg 300
aagaccatcg tcgatccgaa gaccggatgg aacgctggcg gccgcagcgt gacggctgtt 360
gaaggtgatg cgatcctgaa gttcaccgtg ccggataaac cgaccggcgt ccttgttggg 420
ttctctgatg gacgcttcga caactcgttc ggccacccga cacatgcgtt cgccttctac 480
cctgaccggt tccgtatcta cgatcgtggt gtgatcatct tcgaagactt cttccggttc 540
accaaccggt acgccatgtc gcgcgtcggc ggccgggtca cgttctacga agtcaacccg 600
aacgatgatt cttcgcttcg ccccatcgtc aatggcatca cgccttccgg cgggacgatc 660
tacgctgacg ccacgctgta ctcggtcggc gacttcgtga acgacccatc gttcggcggt 720
aactcgtctg cgcagctcaa tgcgctggtc ccgcgtcttc gcccgaccat ctacgaagcg 780
acgtatgccg gtgttgattc tgaacttccg cggatggtac tgatcgcaga tgccgtcgag 840
ccgcaggtta tcaacggtat cgtccccatg ccactgggga acatttcgaa ctactccggc 900
gctaccctgg tgcggactct accgcgcttg gtgcttcaag ccggtacgtc cgatttcgtg 960
gctccatggt cctacgtctc ggcgcatatc cctcgaccgt tcgggagtac caccatcctc 1020
accggcgaag tgcttggcct ggacaacacg atcccgacgc cgcagcggtt gatctcggat 1080
cgtccgtacg cagaagccgg tggcaagtgg ccgtctcggt acatcatcga cgtttgggaa 1140
aacctctggc cgccgggcac cctgatggtg ccggagccga tgcctgtata cagcactgcc 1200
atgctcgacg cacccgtgct gctcatggtc acggacggca tggagatcag cggcaccatc 1260
gacttgatca tgctggtcag cctggatgcc tacgactacc tcggcctgaa cacgacgttc 1320
actctggaaa gcaccatcga actgatgatg cgcgacgggc tggcggtcta ctcgaacatc 1380
agcaccgcgc gggagactgc gctccagtac gccgtcaacg tgctgaccgg cgcgctgacc 1440
acctaccaga atttcggctt caccggcttt gcccgcgtgg gtaatgacac gttcgggatc 1500
aagaacgacg gcctgtatcg cctcgaaggt gagacggacg atggtgaact gctccgcgcg 1560
ttgatcgact tcggtgctga cgactacggc gtgaagaaca ccaagcggtt gtcgagcgcg 1620
tacgctggta tcaccacgga cgggcgtgtg tacttccgca tcaccggcga tgacggtgaa 1680
gagcgcgtgt acacccttgc cggcgaaagt cctgagttcc gcacgccgga tggtgttgcg 1740
aaaggcgtcg ctgctcgcca ctggaggctt cgcctggaag tcgaagacgc ttcgttcgcg 1800
gatctggaca acatcgaagt ggaggtcggg gtttcctccc gcagaatcca tcggaggaac 1860
tga 1863
<210> 6
<211> 444
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 6
<400> 6
atggcactga agtacagctc tggtctgcgc aattcgatga tcgccgacca acctcttcgc 60
aacctgctga ccggctcggt aatccgaatc tactccggct cggctccggc caccgctgat 120
gctacgctcg gctcggccgt gctgttggta gagatcagcg tgaacggctc cggcaacggc 180
gtgagcttcg aaagcaccgt cagcaacggc actttgacca aatcgctgtc cgaggtctgg 240
aacggcacct gtgttgcgac tggcactgca tcgttcttcc gcatggtaca gcccacggac 300
gatggatcgg cgagcaacat cgatccgcgc atccagggca ccgttgctgt gagcggcgcg 360
gacatgaaca tcactcagcc taacctcacc agcggtgcgg ttcagtcgct ggaatacttc 420
tacctgacca tgccggagtc gtaa 444
<210> 7
<211> 1197
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 8
<400> 7
atgagcatcg agacgcgcga caactgggcc agcgggtcca acaacatcgc caagccggag 60
cggctgccgg agaactccgt cgtcaaggcg atgaacatgg atcccaccaa cggtgggaaa 120
ttcgagctgc gtaccggctt cgtcaaggtg aatgactgcg ccgctggccg ggccgtgttc 180
ccgctcggca cggccattct gttcgtcgat ggcggcgacc tcaaagtatt cgacgccagg 240
accaaccagg ggcatgtcgt cgggtcggtt aaccccaacg gtgaagtggc cggctgcgaa 300
cacaacaacc agctgtacct gtctaccccc accgaaagcc ttcgtttcga cggcaacacg 360
gttcggaagt ggggagtgcc gtcgccggta tacaccatca gtctcgtcga cggccacttg 420
ccgaccggaa cgtacaaggt ggctgtgaca gcttatggcg agcagggtga agagtccggt 480
gctgacgccg ttgccgtgtc cgtaccgggt ggtaaagcga tccagatttc gtgcaacgac 540
ccgcggtcct gcacggtgta ttgcagctct gtgaacggat cgacgttgta cgcccagggg 600
ctggtcagtc tgaacacgtt catcatcacg tccacggtgg ataacactca gcggttcact 660
accgacgaaa tgacccctat gccgccgtgc tcgctccttg tgtcgcacca cgctgtcatc 720
gttggggcct acaacaacat catcgtgatg accgagccga tgtggccgca cttgaccaac 780
cccatcactc gattcatcca gctaccgcgc gacatcacca tgctcgccag cgtcgacacc 840
ggcgtgttcg tcgccaccga cgaggaaacc tactggctga ccgatgtcga aacggacgag 900
ccgagttcgg tgcgcaagac gaacttcggc gcagtgcgcg ggaccgctgt caagctgccc 960
gatggccgcg cggcttggtt tacccggtac ggccaagcca taggcgacgc cagcgggaac 1020
attgaactgc caaaccgggt aaactatgct cccgacattg cgactgatgg tgctgccggc 1080
gtgctagaac acaacggtaa ccagttggtc gtcactaccc tgaaaggcca aacgaccacc 1140
aattcactcg gagccggaga tttctggcag cttgaggtaa tcgacaatga ccagtag 1197
<210> 8
<211> 624
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 9
<400> 8
atggtcatca gtaagcagca gttcgaggcg ttgttccctg acgctcccga cgaagtattc 60
gaacccctgg tacgcagcat ggtccgctac gacatcacgt cgacggcgcg tgctgcggcg 120
taccttgctc aaatcggcca tgaatcctcc ggcctcaccc gcttcgaaga aaatctcaac 180
tacagcgctg cccgtttagc cgctgtgtgg cccagtcgct acaaagcaca cagcggtggc 240
cccaacgccc tggctacgca aatcgcgcgc aacccgcaag ccatcgccaa caacacgtac 300
gccaaccgca tgggcaatgg cgacgtgctc agtggtgatg gctggcggta tcgtggtcgc 360
ggcccgttgc aggtcaccgg caaggatggc taccgcaggg cacaggtcat gaccggacgc 420
ccgttcgtag atgacccgga catgatggcc acctacgacg gcggcctcga agccgccgcc 480
gctacgtggc gagacaaggg ctgcaatacc ctggcggacc agggtcggtt cagcgagatc 540
acccgccgga taaacggcgg gatgaatgga gctgaggaca gggaaaaccg ttggcagaag 600
gccaagaagg tactggcgca atga 624
<210> 9
<211> 660
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 13
<400> 9
atgggcaccc gtgtagctga tcttgtcacg acgttccggg aagaaatgcg ggataaggtc 60
cagccttact tctggtcgaa cgatctgctg gtcagctaca tccgggaagc tcagctgaag 120
atcgccgaga aaaccctctg cttggtcggc cagttcaccc ttgaggtgga gcctgggacc 180
ggcatcgtca tcatggacga ggcgatcatc cgtcctcgcc gcgcctggat cgaatcccag 240
cgcggcgaag tcgagatcaa ctgcgtagaa gatcagctcc cggcattcgg cgtgcaagat 300
gcttggaact gccacggcag caaccgtacg ttgacggtgc agttcgacca gcaaggcgat 360
gtcgaactgg cgctctaccg ccccaagccc aacaccgcgc tccagctcac tatcgctgcg 420
taccgtcgcc cggtatgcgg cctgacgatc aacgacaagc tggagatcaa ttctcggtac 480
gaccgtgccg tgctgttcta catgaagtac ctcggcctgc tcgtacaaga cgctgaggtg 540
ttcgacaagt cggaatcgaa tgagcaactt cggctgttcg gcatggaact cggcgacatc 600
aaagagtcgc aggccataag ccaccgctcg ttccagccga ttcgctacaa cgagtattag 660
660
<210> 10
<211> 450
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 14
<400> 10
atggctggca aaacccccgt ccagaacacc gtccaatacg tctccctgac cgatcaggtc 60
gtggccacca tcactgggca cgcgtttcgg ttcgaggccg gcgtaccgcg ttccatcccg 120
aaccacaacc tcgtgctgaa ggctgtacgc gaagctggtt gcgtcgatgt gaacagcatc 180
accgacgaga agttgcgcgc ttccctgaag ctcaccggcg agccgggcac cgctaccacc 240
gtagaccagc agatcgacaa caacgcggct gaacgcgtcg accagatcct ggccgccatc 300
aagactctgg tggatcgcgg cgactctgcc gacttcgcct ccggcggtaa gccgaagacc 360
gaagcaatcg cctccatcac cggcttcgaa gtgaaagccg ctgaacgcga ctccgcctgg 420
aagctgtacc agaccgacaa gccggagtaa 450
<210> 11
<211> 432
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 15
<400> 11
atggcaactc tggaaaacac cgcacgccag tacccgctgt tcatcgagca gaccctcgat 60
ttcagcgatc tggtcgacgg tcaggccgct accctgaccc tcgaattgca aaacggcgcg 120
atcctcgtcc cggagatcag caagctgctg gtcaccaccg catcgaacgc tgccggtgct 180
gcaaccctgg acatcggcgt catcgagccg gggctggcag ccgacccgga cggcatcgcc 240
gccgatctgg atctgaaaac caccggcgcg aaagtcctgg ctccggccaa gctgacctac 300
ccgaacggcg cagtgatcac cttcactgct accgcttcca ctggtggcac cgccggtaag 360
ttcaagttcc tgctggccta catcgtcgaa ggtcgcggca acgagactta cggctccccg 420
gcgtacaact ga 432
<210> 12
<211> 1131
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 16
<400> 12
atgccgttgc ccgtccaagg taactacacc aactttgcgc gcctgaccaa cgaacagaag 60
accgtatggt cccttcagtt ctggcggcaa gcgcgtaacg ccgcgttcat caacatgttc 120
ctcggcaccg atgccaactc gatgatccag cagatcaccg aactgcgtcg tgacgagaaa 180
ggcgcacgcg ccgtaatcac cctgatcgct gacatggttg gcgacggtgt ggtcggcgac 240
aaccaactgg aaggtaacga agaggcgctg accgccttcg ataccgtcat ccagctggac 300
cagatgcgcg ccgccaacgt ccacgaaggt cgcatggccg accagcgttc catcgtcaac 360
ttccgtacta ccagccgcga catgctggcg tactggctgg ccgaccgtat ggaccaactg 420
gcgttcctgt cgctggccgg cgtgagctat gcctatcgca ccaacggtgc gctgcgtggt 480
agctcgccgt tcccgaacct caccttcgcc gccgacgtta ctccgccttc ggccaaccgt 540
cgtctgcgct gggatggcac caacaaggtg ctggttccga acgccgccac ctccgacgtt 600
accgccgctg ataccccgag ctacgctctg ctggtcaacc tcaaggcgta cgcgaagacc 660
aagtacatcc gtggtctgcg cggcgacggc ggcgaggaaa tgtatcacgt gttcctcgac 720
ccgctggcca tggccaagct gaagctggac ccggactaca tcgccaacct gcgtagcggt 780
tacacccgcg gcaacgtgaa cccgctgttc aagggcggca tcgtgaccgt ggatggtctg 840
gtgattcacg agttccgcca cgtgtacaac acccgcggca tggctccggg tgccaagtgg 900
ggtgcctccg gcaacgttga cggctgctcg atgctcttct gcggcgcgca ggcgctgggc 960
ttcgccgata tcggcaaccc gcgctgggtc gagaaggaat tcgactacga caacaagcac 1020
ggtatctccg tggcgaagat cctcggcttc ctgaagcctc agttcccgtc gatctacgag 1080
gacggtaaca ccgaggactt cggtgtcatc aacgtgtacg tggccgccta a 1131
<210> 13
<211> 1881
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 19
<400> 13
atgccgaata cgtcgagtga gcgtaagccg cgctggcact gctcgaagtg cgaatcgccg 60
atctataccc ccaggcacag caccgggatc tgtctgtcct gccgcgtcgc cggccgaggg 120
aacaagatcg tcgatgtagc gaatgatccc gtcgataccg tcgataccgt gccgatcccg 180
aaaacggcca agttgaagaa agaccggatc gacaagaaga agccccgcgc caacccgaag 240
atcatgcgcg agaacacgcg gtcgaattcg gcccacgtga tctacgagga cggcagtatc 300
ggggtcgtca gccgggatag ccacgagtac cagctggccg ccgcgcagaa gatcatggcc 360
gagcgcacgc tcatgcgccg gcggttcctc ccgttcgtgc agaagatgaa ctcgaagtac 420
gaggtagccg tcgcccacga gatcctggcg cgcgtactgg agcaatttct cgacgactcc 480
atgaatgggc ggtcgccccg cgtcatggtc acgttcccgc cgcggcacgg gaaatccgag 540
cagaccagcc ggaagttccc ggcctgggcg ctggggaaat acccggaggc agggatcatc 600
ctggccagct acggcatgga cttggccgag aagatgtccc gcgacatcct cagcacggtg 660
aagagccagg aatacaaggc gatcttcccg gacttggaac tggtcaacga gcgtatcgat 720
gactgggcca cgtcgaaagg cggcggtgta cgtgccgcgg gcgttggcgt cggcgtgact 780
ggtatgggct gccacatgct gatcatcgac gacccgttca aggaccggga atcggcggat 840
tcggagacga tccgggagaa gacttgggac tggtacacct cgacggcgct gactcgtttg 900
acccccggcg gcggcgtgct gctgatcaac acccgctggc acgatgatga cctgtccggc 960
cggctctgcg ccgcgatgca ggaagatcct gagtacgaga aatggaagat cgtcaacttc 1020
gctgccttgg ccgagaacga cgagtggctg acccaggacg atacgatcgt cgactcaccg 1080
ctgcccggcg ccgtaccgtt caggaaggcc ggggaagctc tgcacgaagc ccggtacagc 1140
cggaagtacc tgctcaatct gaaacggatt ttgcacgcac gggactggaa cagcctgtac 1200
cagcagaacc cggtgccgga cgacggggaa tacttcaagt cggactactt catcgagcac 1260
gaccctgggg acgagcgcta cgacggcacg gcgtacatcg ccgtggactt cgcgatcacc 1320
gagaagcaga ccagtgacta caccgtcatc gccgccgggt tgcacatgcc gaacgacacg 1380
atccacgtcg acgacatcat ccgtatgcgc acgggggaca gctcgaaggt ggtcacggcc 1440
atactcgaca ccgtgcagcg gtacaagtcg cacaaccctg tcctgggcgt ggaagatggg 1500
cagatttgga agtcgatcag gccgtacttc gaagccgagg ccaagcggcg gaagatttac 1560
gtcaaggttg agctgctgaa gccgctgacc gataaatcgg cacgtgcccg gccgctccag 1620
ggccgtatgg cgaaccacat ggtcacgctg cgccgcggcg ctcgctggat cgagacgatg 1680
aaggctgagt tccttcgatt cccggtaggc cggcacgatg atatagtcga cgcgcttgca 1740
tggatggcac agctgatcct tactaagaac ccaccgctcc ctctttccgc gcgccggccg 1800
cgtcgcgggg atcgcaccgt tgcgcagcag ttgtccgaca tcctgcgcgg cgtcgggaac 1860
ggcagtcaca tgagcgcatg a 1881
<210> 14
<211> 1476
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 48
<400> 14
atgtcgaaca acgccaccgt caagaaagcc gtcaagtcgc tcagcgagat ccccgagcag 60
caccatgtcg ccgagatcgt ccaccacggc gacaagctga ccctgcccga aggcatgggc 120
gtcagcgatg ctatcgagct gctggagcgc cgccgcagct acctcgaaga agctgtcggc 180
ctgacgcgca ccttcaacgt cttcccctgg gacggcgcga acgccatcaa catcgccctg 240
gcgcgtcgtt tcggctgggc cgccgccgag gctactcctg gcttcttcgg cagcactccg 300
ccgaagatga tcaccatcga agtcggccct ggccagaccc gtcgtgtacc gtggggtcgc 360
ttcagcatgc cgggtatcga aggcttcgtg cagaccagcg ccagcatgaa agacggccgt 420
ctgtgtttcc agctggtcgc gcaggttctg cgtaaggacg agcagaccat cgagaagctg 480
ttcgatgaag tcgaagacgt gctgaagcac gagtcgatct acgccggtaa ggcgatcaag 540
atccgcttcc gtgacgacga cggcaacacc ctggaaatgc ccgagccgaa gttcctcgac 600
gtgagcggcg tgtcgcgcga catgctggtg tactcgaaag aagtcaccga ctccatcgaa 660
accaacctgt tcacgcccat cgagcgcgtc cacgactgca tcaagaacgg tatcccggtc 720
aagcgcggcg tcctgctggg cggtccgtac ggcaccggta agaccctggc cgccaccgtt 780
gcatcgcgtc tcgctgtcga cgccggcgta acctacctgt acgtgccgcg tgcggacgaa 840
ctggccgacg ccatcgagtt cgccaagcag taccaagacg tggcctgcgt gatcttctgc 900
gaggacatcg atcgctgcat gagcggcgag cgttcggtgg cgatggacga catcctgaac 960
atcctcgacg gcatcgacac caagtcgtcg cggatcatca ccgtcctcac caccaaccac 1020
ctgaccgaca tcaacccggc catgctgcgc cccggccgcc tggacgcgat catcgacgtg 1080
gttccgccgg atgcggaagc tgtcgttcgc ctgatcaagc tctacggcgc tggtgacatc 1140
gacgagcagg ctgatctgac cccggcggcc gagctgctgg ccggtgcgat tccggcggtc 1200
atcgccgagg tagtcaagcg ttcgaagctg gcccagctcc agctgcaagc gccgggcacc 1260
gcgatcgaga agatcaccgg cgacgcgatc ctgctggcgg cgcaggccat ccagagccaa 1320
gtcaagctgc tggccgagca gtcaatgccg cgtgtggctc cgctcaccat ggacagcctg 1380
ctgcgcaaca tcgtcaagga cgagttcgaa gcgctcgcaa ccgaactgga cagcattcgc 1440
caactgtccg aaagcatccg cgaacgcgta agctaa 1476
<210> 15
<211> 729
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 62
<400> 15
atgcgctggt cgatcagtaa gctgcacgtc cgcgaaggct gtgcataccg ctacaaactg 60
aagtacatcg acaaagttcc cgaacctgaa cgtcccctcc cccctggtaa gtctgagcac 120
gcgaacgacc gcggctctcg tgtccacgag cagaacgaac tattcgttcg cggtgaagtg 180
gacaagctgc cggcagaatc tgctgacttc caagccttga tcgaagacct gcaagaacgc 240
ttccgcgccg gcttggtcat gctggagcat gactggtgct tcgacgaaga ttgggaaccc 300
tgctcgcccg aagagcgggc cgccatcgcc atcgtcgacg tggctgtctg gatcgttaaa 360
gatcgctggc tcctgatcat cgattacaaa accgggcgca agtacgaaac caagcacatg 420
gaccagatgc agctctatgc cctggccgcc ttcaagaaat ggccgttcct cgaacgagtc 480
accaccgaac tctggtatct cgatatcgac gagatatcga ccagtcactt cacccgaaac 540
catatcccgg ctatccagcg cgcgttccat aaccgcgtcg ggaagatgga acgggacacc 600
gaattcaaac cggccgcgaa tatctacagc tgccggtact gcccgtacaa ggacgggatc 660
tgtccgcacg cggtagacga aaaaacgccc gtgaagggca acgaatgggc ctctgagtgg 720
aagatatga 729
<210> 16
<211> 1362
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 64
<400> 16
atggcaaagt tcaaaccgat caaactgatg ccgcaccaga agaagacgct gaagaagcgc 60
ggcgaaactt cgatcttgct ggatctgtcc gaaccgggca ccgggaagtc cgtggcgcat 120
gcgacgcact tcgtgaagca tcggcaagca ggcggcggcg ctgggttgat cgtcgcgccg 180
ttgtcgttga tcgatacggt atggccacac gagatcggcc tggtgaaccc ggacgtggat 240
gtgagcgtag cgttcgccac caaccgagcc aaggcgttcc agcctgggca cgacatatat 300
gtcaccaact acaacggcct ggagtacctg tccgaaaacc ccagcctcat gcggaagttg 360
ggaatcgatt ggttcctcgg cgacgaggcc actgccttca agaacccgca ggccaagcgc 420
acgaaacgct gccataaact ggttcggaac gtcgagttca aagcgctgct gtccggttcg 480
ctcggcgcga agatgatcac cgattacttt gcaccgacgc tgatacttga cgatggtaaa 540
cgcctgggat ggcagttcag ccgattccgc gaagcaacct gctacccggt gcaagttggc 600
cggcaagcgc acatgatcca atgggagccg cgcgaaggcg cagacttggc cgtggctcag 660
ctcttgcagg acatcagcat ccgtcacctc ttcgccacca cggtgaagca gagcatccgc 720
acgatcgaat tcaagctgcc gccgaagctg cgcaagttgt acgagcagat ggcgcgggag 780
caagccatgt tcctcaagga caaggtgatc accgcggcga acggtggggc agccgcgcag 840
aagttgctcc agatcgccag cggctcgacc tacgacaacc agaaggccaa caccctgctc 900
gacatgcagc ggtacgaact tgtcgccgat ctggccgagg aacgcgaaaa gaccctgatc 960
gcgttccagt ggcaccacca gcgtgaagcg cttgagctgc tgctgaaaaa gcgtgggcgg 1020
accaccgcat atatcgatgg caccgtaccg ggcgagaagc gcaaagctat cgtcgaagcg 1080
cacaaacgcg gtgagatcga tgacctgctt cttcaaccgc aagcggctgc acacggcctt 1140
accctggtga atgccaggac tacgatttgg gccacgccga cctacgacta cgagctgttc 1200
gaccagctca accggcggac ctatcggact ggccagagcc aggattgcga agtcatcgtg 1260
atatgcgccg agaacacact cgacgccaaa gccttcgagg tctgcacgac caaaggcaag 1320
cgcatgatga cgatgttcga gtacatccgc gacttcacgt aa 1362
<210> 17
<211> 1965
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 65
<400> 17
atgacgatta tggttccgcg catccatgac gggatgaaac ccgttacgct gcgcccgctg 60
aaaaagttca aaccgctggt ggtcgacttc gaaacctact ggggtccgaa gtattccctg 120
cgcatgatgt ccaccagtga ctacgttcgc ggtgaccagt tcaagatcca ctgcgtaggt 180
gccaagctgg gcaacgccaa gacgcgcatc ttcaccgaca tgaagaagtt cgctgcgtgg 240
ctggctaagg tccaggctga gtacgagatc gagttaatag gccacaacct gtacttcgac 300
ggcttgatcc tcagcgagta tttcggattc gtgccggcgg cttaccgctg cacgatgtcg 360
atgtcgaaag ggctgttccg caacaccatc gcgcacggcc ttgacaccgt agcgaagctg 420
ttcggcctgg ccggtaaagt aaaggcccag gccaacgtga acacgttcgg caaatgggat 480
ctcacgcggc acgagttgag tgacctcggc gaatactgca tcgacgattg cgaagacacc 540
tacagaatct accaggccat gcgtccgtac ataccggacg atgaaatgga catcatccac 600
gacaccgttc gttgtttctg cgacccggtg cttcgcgtga acggaccgat gctcgaagaa 660
gcgatcgccg aagtcgaagc caagcgtgcg gtcttgtaca agcaagcgat cgaactggtg 720
aacaccctcg ctccggggct ggtcaacgcc aagcgcccgt tcgagacggt gctgcgatct 780
gctgtcgatt tcccgctgct gcttgaagca ctcggcgttg aagtgccgat gaagcagaac 840
gataaaggct tgtggatacc agcactggcc aagaaagaca cagggttcgt cgagctgtgc 900
gaagaccctg atcctctggt ccgtctcctg tgtgaagcgc gacttcagtt cacgtcgaac 960
cagaccgtca cgcgtgcgca gcgcctgctg gacgctaccc aggacggagc actgctgccg 1020
gtgatgtacg gctactgcgg cgcattgtcg atgcgctgga cagccggcaa caagatgaac 1080
ctccagaacc ttcagcgcgg gtcggcactt cgccgagcca tcgaagcgcc gaagggctgg 1140
cacatcatga ccggggactc ggcgcagatc gaagcacgga ttctggcgta catagctggg 1200
cagtgggatc tggtcgaagc gttccgcgtc ggcgcggacg tgtactccga attcgccatg 1260
gagatttacc cggatgtcga ggtaagcaag gaaaacccgg atacggaaac cgagcgtcac 1320
gtaggtaaga cttccatcct cggcctgggt tacggcatgg ggttcaggaa gttcatcacc 1380
acgatggcga ccagcttcat ccccgtgctg atggaagtcg aagacgccaa gcacgtcgtg 1440
aacacgtacc gcacgaagta cccgatgatc ccggcgttgt ggaagtacct cgacagcatc 1500
ctggccgata tggctgctgg taacagcggg ttcatcgagt tccagtgcgg gcttcgcctg 1560
gaatacgaac ctgaccggat ctggatgccg aatggcctgt gcctgcatta ccccgaactc 1620
cgtgaagagt acgacgagga cactgggcgg aagaacggct acacctactc gatcgtccgc 1680
gggaagaacg tcagccggaa gaaaatctac ggcgggctgc tgactgaaaa catcgtccag 1740
tgcttggcgc ggatcgtagt gggtgaccag atgcggctca tggcgaaagc ctaccgtgtg 1800
gtcatgacca cacacgacga agtgtcgatg ctggtccggg ctacgaagac ggcgctggcc 1860
aaggccacga agttcatggt gaaaacgatg tccactgcac cctggtgggc acctgacctg 1920
ccggtggcga ctgaagtgaa ggacgccccg tactactgca agtag 1965
<210> 18
<211> 540
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 73
<400> 18
atggcaaagc aaatacctac ggaactgtct atcgacctgg aaaccctcgg aacctccgtg 60
gaatcggtga tcctttcggt ggcgatggtg acgagcaccg gcgaaaagtt ccacatagca 120
atcgatccgt ccgagcaaat cgccgccggc cgtaaagtcg atgcgagcac gatcatgtgg 180
tggctcggcc ccggcgctgg tgaaccggcg cgcggggcaa tgaccgaact catggccaag 240
cggaagtacg gcatggaaga cgccaagctc gaaatcatgt cgttcctcga cggcgtactg 300
aagaaaaacc cgcgcgtgcg cgtgtggggt aactccccgt cgttcgactg cgaaatgctg 360
gcgaatttcc tcggctgtaa accgtggctc ttcttcaacg agcgcgatgt tcgtacggca 420
cgcatggtgg tcgggcgtac ccaggccagt accggacacg acgcgctggc cgacgcagaa 480
gcgcagctcg tcgacgccat gcgtttcatc gaagtggccg acaaggaggc gcgcaaatga 540
540
<210> 19
<211> 393
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 79
<400> 19
atgaacctgt cctgggactt catgaagtcc atcgctgagc gggaaagcgt gaaagaggta 60
ctgtcggaat tcctcaagga atcgacgctc aaagtgaacg gcgctgacgc actgctggtg 120
ctgcacatcg tatcggcgta caccacctgc gacggcagcc acggcgggcc agcatgtggt 180
gaccctgatt gctgcgccaa tcagaaacct gacgacgcga aaattcgcat gcagttggaa 240
cgcgccgtga atgcattgcg tacgttgtgt aacgtcgaca cgaaggaaga catcgatgcg 300
atgctgctcg ctatgcgtgc catgcccggt gacttgaacg accgcatcgc ggtcatagca 360
accttggaac tactgaagga gctgatggaa tga 393
<210> 20
<211> 303
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 82
<400> 20
atgatcatca agttgtcgcc gtatgcaccg ctccccgata gcaacgagca cctgtcgctg 60
agcaggactg gtgatgtact cactgtgaac ggtcaggagt tcgattttac gccgctcccg 120
gagggtggtg agttgccgtc cgaggctatt gagtcggaat ggttcgtcgg tcctgtagta 180
cgaagaaacg gccggctgga gttgactctg cgctacccgc ttgacgtgga tgctagcgaa 240
gccgctagat tccctgagcc gttgcttatc gaggccgatg gcccggtgga gttaccgaaa 300
tga 303
<210> 21
<211> 957
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 83
<400> 21
atggctgacg caatccccct caaggtaatc gacaacggcg gcggcaacgg gaacctgtcc 60
cagttcgccg ccagcgacac cgtacctatc accaacggcg ggactggcgc ttccaccgca 120
accgatgcgt tcgcggccct ggccacggca cgggtgaaca acttcgcggg tctggccggc 180
ggaacggacg tgctgccgta tcagaacggt gcgaatacct gggcgcaaac gccgatcacc 240
gccgtaggcc gggcgattat caacgccagt acgcaggcaa acgccttgaa ctatatcggc 300
ggcgtaccta aaagtatgtc gttcaaccgg gccgtctccg acccgaacac ggtccctgac 360
gaatgtgggt tctacggtat cggtacgtcg ccctggtcga atctgccgcc gggtatcgat 420
tcgctgaacc ctattggttc tatgctctac caccacccct acgacgcagc aactgcggtg 480
cagctgttcg taccgcggac ttcgaacatc ttctatttcc gacgcaaggg atctggtact 540
tggcagccgt ggattcgcgt gctgtccgat gcgcagcttc ttggtacggt agctcagtct 600
ggaggctcgc cgatcggctc tattcttgag cgaggcagca acgcgaacgg ggaatacatc 660
cggctcgcag acggtacgca gctctgctgg ttcaacgcca gcgttaccga tcaggcggtc 720
gataccgctt acggcagctt gtttaccggc actcgtgggt ggtctttccc tgcgacgttt 780
gtcggtagcc cgacggtgag tgtcggtcta tttcgctggg ggactggcgc aggctgggga 840
accgtcggcg gggttgctag tacgaccagt gtgacgctgc ggatattcga catcgcttcg 900
agggcgaccg gaaccgcgac agcaatctct gcgatagcca acgggaggtg gttctga 957
<210> 22
<211> 678
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 86
<400> 22
atgaacgcag gtcaggctct agtcgtccgc cgggtcggcc agtgcctgtc cgtggcggta 60
tcgacaccgc aggcgcttgt caccagggag cgctctcagg cgctgcttgt gcgtgacccc 120
gacatggaga tcgtcctgcc cctggcgcgg ccagcgtcgc aactggagta caccgccatg 180
gtcctgccgc ctgcgcaggc cgtcaccgag gtgctgatcc agccgggggc gcagcaggtg 240
caggacttgc gctcggcggc gttcgtcgtc ctggccgggc agcctgggcg caagggcgac 300
aagggtgaac ccggcccggc cggcggcgcg atcatccaga aggtggcgtc ggtgccgatg 360
tccgggcatc gcatggtcgc accgatcgac gccaaccaag tggtgtacgc tgattgcgcg 420
acgctgatca atcggataaa caccctgggg ctgtcgctga atgcggcgtc ccctggcggc 480
acagtggatg tgcagcgcct cggtgaagtg cagcactccg ggtgggcgtg gacacccggt 540
gccgtgttcc tcggccagga tggcaatctc acgcaaaccg ttccctctgg cgcgctgttc 600
tcgctgatcg taggcttcgc gctcgaccct actactctat ttatcgacat tggcgtggcg 660
atcacgctgg aggtgtga 678
<210> 23
<211> 4878
<212> DNA
<213> Unknown
<220>
<223> bacteriophage specific for Pseudomonas
aeruginosa(YMC17/07/R4900a_PAE_BP) ORF 88
<400> 23
atgcgaccgc aggatctccg tcagctgtcg aatgcgttgc gtgtcgaact caccaccggc 60
accggcgagc tgcaaccgtt cctcgaacgc gccttcgcca acccgcagca ggtgctcgac 120
ggcctggacg ccagcctgcg cggtgagtcc cccagccgta gcacaagcga ggtatccgat 180
gctccccaat ctgctggcgc tcttgacgat gaacttgacg gcggggagtt cgaccaagct 240
cgaaccgtcg agtccgccgc cgagaactgg ttcggcgata ccaccggaaa ccgccggatt 300
caaactggcg gcctcggtat ccccgcccca atcgcccgtg ccgatacgca acgacttcag 360
cgtgccgaag aagcagctcg aagagcgaac ccggacgggt ctatcgagcg cgtgcccgct 420
gaacgagcct tgcgcgaact cggtgtcgat cccgcagacg ttgcagcaga acttgggctg 480
tcgcctgacg ccctggcaag ttcggtcctt gttcgggcag tccgacccga cgctacgggt 540
gcagcacaag cccttcgcag cgtacggcag cttcgtcgtt ctaccgttga gcggctgaac 600
caagagccga acaacccgtc cgccggcagc tacatcgctg ccacgacgcc ggagggcacg 660
aacgtagccg tggacctgcg ccgtctggta ggcgcgcagg tattcggtcg tcgtgacgcc 720
caggcgctgc gtgacgcttt gtccgatggc ctgggcaccc tggccgacgc cggctaccag 780
ttccagttac cggacaccgc cgtggtggcc cggtacaagg acgggagcgg cgaggtagca 840
gtcaccgtgg cggacctgcg ccagggagca gaccagccgc gcgccggcct gcctcgtgat 900
gccatcggcc tggatagccc gaccgccgaa gcgctccaag acttggtaca aacgtacgaa 960
aacccggagc gaaccgtgca atatgcacga caggcggacg ttgagcgctt gatcgacgaa 1020
tacgccgtcc agacgctcct gggagcgctt cagcggcgag ggggcaccgc taccattccc 1080
gaagccgcag cgcgtctcct gcgcgctgcc agcccccgtg gcgtggctct ggagggtaat 1140
accgccaccc tgaccggcga accactgcct ccggccatgg atttaggctc cctgcgcacc 1200
cccggcagcc ccatcgacac cctggccagg accgttgccg accgcggccc aatgcgcgaa 1260
agcctacgcc tgctggccca gggcgctgcc caggcccaag acccgtccgt gcgcgacttc 1320
tggcagcgcc aactcgaccg ccggcctgct ccggtggaca acaccggcac cgacgagcag 1380
ctgcaacgcc ggaacctcga agatttcgct gcccagcagg gcatgcagga actcgacccg 1440
gagcgcatgc aggcgcagac catcgaagcc gccaccgggc aggaaggtgc ggccgcgcgg 1500
aacgaaccga cgccgatagg ccgccgccgg cctgggcctt ccccgctgga cttcggcgcg 1560
cacatgaaca acgtcgccgc cagcgtgcag cagcggtcgt ggatgaacac cacgcagacg 1620
aacgtaccgg gtgcctgggc cgcgccgatg gccgcagcca tgaacggcac gccgttgaag 1680
gtcgctttcg ccttgaaccg tagtgaggtg cttcgcagcc gcgacgccac gaacctgatg 1740
aacgcctaca cgcgccgggg gttcaccatc agcgggacca gactcgacgt ggatcaggat 1800
accggcccgt acagcaagag cgcgtacgcg cggatcttgg ggccgaccgg aaccgacccc 1860
gtggatgtgg tgatcaccgc cggtgccagt acccccgccg tcatgctggc tcgccggatc 1920
ggcgtgcccg tgctcgacat caccgtgccg gcgcaggcaa agatcgctgg tgatctggcc 1980
cgtgccttcg accgtgccac gcgcgaagac ctgcacaacc gccgggagtc catgaacccg 2040
gcggcgaacc gggaagcccg ccggagcctc gacactcgcc agggtgttca gcgcgcgcgg 2100
gacatcctcg gcgcagggat cgacaagcag ctgtcggcac aatgggctga cccggcagcg 2160
actgagcgtc ttctgcgcct ggggcgcttg tcgttcatcg ccgacgacgc gttcttcgag 2220
gccgggctgg ctggccgctc tgtgacgtac ctgtccgata acatcgacgc gctggaggcg 2280
tatcaccagc agtacctcag cgagacttcc cagcagagtg cccggccgca gggtgcgagc 2340
caaatgagcc agcagcaagc caaagacctg aacgactaca tcactcgcgt gctgccgagc 2400
gatgtcatgt tcagcatcga gaggctgccg ggtatcagcg gtatgttcac cgagaaactg 2460
gaccctaccc gcccggacat caacgggaac ccgaccatgc agcggttcat caaggtagcg 2520
gtcaacgccg ccagcccgat gtccacggcg ttccatgaat ccatgcacgc gttgatttcc 2580
gtccttcgcg ggcagaagca gcaaagccag ttcatcaagg cgctggaccg cgcagcgagt 2640
aacccggtgg tgctcggcaa gatgcgctcc ctgctggcca acgaaccggc cgcgctcgaa 2700
cagctcagcg acccggagga acgcatcgcc tacatgtacg agttgtgggc cagtggcatg 2760
ctcgacatcc aggcgcagcc gcagacgtgg atgtcccggt tcgctgggtg gattcgcggc 2820
accttgtcga tcctgaacaa cgagcagaaa gccgagctgt acctccaggc attcaaggat 2880
gggaagctgc gccggccgag cgctgtcaac cgcgtggtga tgcagtccct gtccggcccg 2940
gagcgcgccc tggtaagcag tcgagtggct gaccgcgtga gtacgctcac cgggaagttc 3000
ctgcgcaccg cgcacggccg gttgaagaac tacggtaacc cggcgttgag caagatcgct 3060
gaccagttct acgcgcgcag cgatacccag ggccaacgcg ccgggtacat ccagaccgtg 3120
cgggaagtga cgaacctgtt cggtacgcag ctggccaaca tcatcaagac catggacgag 3180
cagcaactgg cggatctgtc cgcggcgctt cacaggaacg tgcgcccgac cgatccggcc 3240
atggcgcaga agtacgacga caccaagtcg ttgctccgtc gcatcttcaa ctacatgaag 3300
gtgtccaacg tcgacgtggc gaacgttcag gactacttcc cgcaggcgtg gagtcgggag 3360
gcgatcgacg ccgacttcga taacttcgtc gatgcgctgg tgcaggtcgg gcaagtacgt 3420
gacgacaacg ggaactggat cgacatgacg cccgacatcg ctacctccgt ggccgagacg 3480
ttgaccacca ccgaggggca actggcgctg agtgaagact tggccggcta ctccccgtac 3540
atgcaggcgg tcaacgaacg gaagatccga ctgaaggatc gtgcagccgt cgcacagtac 3600
atggacccgg atatcgtccg tgtgctgacc cgctacgtca cccaggctgc gaagcgtggg 3660
gagtacacga agcacttcgg acggaacggt gaacgcctga aggaccagct gcaagaagcc 3720
aagcggtacg gcctgacgga cgagcagatc gaacgggatg tagcgccggc tatccgtgcg 3780
ctcgaaggca cgctcggtag caacatcgac ccgcacctgc gcagcgccat gtccggcctg 3840
atcacttggc agaacctcgt cgtgctgccg ctgtcgattt tcagctccct tatcgacccg 3900
ctgggcatcg tcgtacgcgg cggggaagtg agcgatgcct ggaccgcctt caaagccggt 3960
gtacggaaca tcccgcagag cctgcggcgc aacggcaaca agctcgacat tcagcgcttc 4020
gctgaggatg tcggcaccgt ggaagagtcg ttcgtgctcg acctgctggg tgacatgtac 4080
ggctccaact acatgtcgga ctgggcgcgc aagaccaaca acctgctgtt caagtacaac 4140
ctgatggaag gttggaacac ggctatgcgc tcggcggcca ccgtcgccgc cgagaagttc 4200
atcattcgcc acgccgcggg cgtcaaccag cacagcacac gctacctcga cgagcttggt 4260
atcaccgcca aggacgtgca gaccgacgcg aacggtcgcc tgctgttccg tgcgcaggac 4320
ttcatcgccc agggcatgaa cccgaaggac gccatcgaga aaagccgtct ggtgcgcgaa 4380
gccatcggcc gctgggtgga cggcgcagtc ctgcgcccgc acgcggcgga ccgtccagcc 4440
tgggccagtg acccgcactg gatgctcgtg tggcacctca agcagttcac ctacagcttc 4500
cagcggacca tcctcgaccg cgccacgcac gagatgcgga acgggaacta tgcgccgatg 4560
ctgaccctgg ccgcgtacgt gcccttcatg atcgccgccg acttcctcaa ggccatgctc 4620
cagggcgcgg gcgatgaacc cgactggtac aagagccagg acgcgggtga actgatctgg 4680
aggggtgtgg aacgcgccgg cctgctcggc gtgcgccagt tcgccaccga tggtatcgaa 4740
agcccggcgt tcaccctcgg tccgaccttc agctacatgc tcaaggccgg ggaaaagacg 4800
atggacgggg acgtgacggg ggccgcgctg agcgctcttc cgggtaacgc gctgtggaaa 4860
gattggatcg atcgatag 4878
Claims (14)
- 카바페넴(carbapenem) 계열 항생제 내성 녹농균(Pseudomonas aeruginosa)에 특이적인 사멸능을 가지며,
서열번호 8의 염기서열로 이루어진 핵산을 포함하는, 기탁번호 KCCM12962P인 박테리오파지. - 삭제
- 제1항에 있어서,
상기 카바페넴 계열 항생제는 아미카신(amikacin), 아제트레오남 (azetreonam), 세프타지딤(ceftazidime), 시프로플록사신(ciprofloxacin), 콜리스틴(colistin), 세페핌(cefepime), 젠타마이신(gentamicin), 이미페넴(imipenem), 레보플록사신(levofloxacin), 메로페넴(meropenem), 피페라실린(piperacillin), 피페라실린-타조박탐(piperacillin-tazobactam) 및 이들의 조합으로 이루어진 군에서 선택되는 하나 이상인, 박테리오파지. - 삭제
- 제1항에 있어서,
상기 박테리오파지는 서열번호 2 내지 7, 서열번호 9 내지 23중 적어도 하나 이상의 염기 서열로 이루어진 핵산을 더욱 포함하는, 박테리오파지. - 제1항에 있어서,
상기 박테리오파지는 서열번호 1로 염기서열로 이루어진 유전체를 포함하는 것인, 박테리오파지. - 삭제
- 제1항에 있어서,
상기 박테리오파지는 포도비리대(Podoviridae)에 속하는 것인, 박테리오파지. - 제1항의 박테리오파지를 포함하는, 항생제.
- 제1항의 박테리오파지를 포함하는, 소독제.
- 삭제
- 삭제
- 제1항의 박테리오파지를 포함하는, 식품 조성물.
- 제1항의 박테리오파지를 포함하는, 사료 조성물.
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| Application Number | Priority Date | Filing Date | Title |
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| KR1020210136865A KR102646232B1 (ko) | 2021-10-14 | 2021-10-14 | 항생제 내성 슈도모나스균 특이적 박테리오파지 |
| PCT/KR2021/014331 WO2023063453A1 (ko) | 2021-10-14 | 2021-10-15 | 항생제 내성 슈도모나스균 특이적 박테리오파지 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR101788401B1 (ko) * | 2015-10-01 | 2017-10-19 | 연세대학교 산학협력단 | 항생제 내성을 갖는 슈도모나스 균속을 용균하는 박테리오파지 |
| KR101789877B1 (ko) * | 2015-10-01 | 2017-10-26 | 연세대학교 산학협력단 | 항생제 내성을 갖는 슈도모나스 균속을 용균하는 박테리오파지 |
| KR101824778B1 (ko) * | 2015-11-26 | 2018-02-01 | 연세대학교 산학협력단 | 항생제 내성을 갖는 슈도모나스속 균을 용균하는 박테리오파지 |
| KR101779262B1 (ko) | 2015-11-26 | 2017-09-18 | 연세대학교 산학협력단 | 항생제 내성을 갖는 슈도모나스 균속을 용균하는 박테리오파지 |
| KR20180073489A (ko) * | 2016-12-22 | 2018-07-02 | 주식회사 옵티팜 | 신규한 녹농균 특이 박테리오파지 pa4 및 이를 포함하는 항균 조성물 |
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2021
- 2021-10-14 KR KR1020210136865A patent/KR102646232B1/ko active IP Right Grant
- 2021-10-15 WO PCT/KR2021/014331 patent/WO2023063453A1/ko active Application Filing
Non-Patent Citations (1)
| Title |
|---|
| Pseudomonas phage KPP25 DNA, complete sequence, GenBank: AB910393.1, 2015.07.02. |
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| KR20230053402A (ko) | 2023-04-21 |
| WO2023063453A1 (ko) | 2023-04-20 |
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