KR20200135145A - Lactobacillus paracasei wikim0110 having antibacterial activity against clostridioides difficile and composition comprising the same - Google Patents
Lactobacillus paracasei wikim0110 having antibacterial activity against clostridioides difficile and composition comprising the same Download PDFInfo
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- KR20200135145A KR20200135145A KR1020200015053A KR20200015053A KR20200135145A KR 20200135145 A KR20200135145 A KR 20200135145A KR 1020200015053 A KR1020200015053 A KR 1020200015053A KR 20200015053 A KR20200015053 A KR 20200015053A KR 20200135145 A KR20200135145 A KR 20200135145A
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- lactobacillus paracasei
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Abstract
Description
본 발명은 락토바실러스 파라카세이 WiKim0110 균주 및 이를 포함하는 조성물에 관한 것이다.The present invention relates to a Lactobacillus paracasei WiKim0110 strain and a composition comprising the same.
클로스트리디오이데스 디피실레 감염(Clostridioides difficile infection, CDI) 질병은 전 세계적으로 잘 알려진 주요 장내 병원성 박테리아인 클로스트리디오이데스 디피실레(Clostridioides difficile)에 의한 감염성 질환이다. 세계적으로 연간 453,000건의 감염이 발생하며, 미국에서는 클로스트리디오이데스 디피실레에 의한 직접적인 사망이 1만 5천 건 정도 발생하고 있다. 유럽과 영국에서는 매년 약 124,000명과 18,005명이 감염된다. 아시아, 특히 동아시아에서 CDI로 진단받은 환자는 유럽 및 북미와 마찬가지로 유병률이 높다. CDI는 보통 복통, 설사 및 발열이 동반된다. 또한 CDI는 광범위한 항생제 사용 후 장에서 발생하는 설사 및 위장성 대장염을 비롯하여 다양한 증상을 유발하며 생명을 위협할 수 있다. Clostridioides difficile infection (CDI) disease is an infectious disease caused by Clostridioides difficile , a major intestinal pathogenic bacterium well known worldwide. Worldwide, there are 453,000 infections per year, and in the United States, there are about 15,000 direct deaths from Clostridioides difficile. Approximately 124,000 and 18,005 people are infected annually in Europe and the UK. Patients diagnosed with CDI in Asia, especially East Asia, have a high prevalence, as in Europe and North America. CDI is usually accompanied by abdominal pain, diarrhea and fever. In addition, CDI can cause a variety of symptoms, including diarrhea and gastrointestinal colitis that occur in the intestine after extensive antibiotic use and can be life-threatening.
또한, 클로스트리디오이데스 디피실레는 장내 상재하는 기회감염 병원균이지만, 장 면역력이 강한 사람에서는 아무런 증상을 유발하지 않으며, 생후 1개월 이내 신생아 장내에서 높은 비율로 관찰된다. 설사나 위막성 대장염(Pseudomembranous colitis)을 치료하려고 항생제를 계속 복용하게 되면, 현재 항생제 내성을 나타내고 있는 클로스트리디오이데스 디피실레 숫자는 장내에서 급격하게 증가하게 되고 이들 세균이 분비하는 독소 때문에 심각한 중증 설사가 지속되어, 이로 인한 독성과 내성의 문제가 발생하여 새로운 CDI 치료 기술의 개발이 요구되고 있다(비특허문헌 1). In addition, Clostridioides difficile is an opportunistic pathogen that resides in the intestine, but does not cause any symptoms in people with strong intestinal immunity, and is observed at a high rate in the intestine of newborns within 1 month of life. If antibiotics continue to be taken to treat diarrhea or Pseudomembranous colitis, the number of Clostridioides difficile, currently antibiotic-resistant, increases rapidly in the intestine.Severe severe diarrhea due to toxins secreted by these bacteria As a result, toxicity and tolerance problems arise, and development of a new CDI treatment technology is required (Non-Patent Document 1).
따라서 클로스트리디오이데스 디피실레에 의한 감염 질환의 개선, 예방 또는 치료의 중요성이 대두되고 있는 실정이다. 이에, 본 발명에서는 효과적으로 클로스트리디오이데스 디피실레에 의한 감염 질환을 개선시키는 유산균에 대해 연구하였다.Therefore, the importance of improvement, prevention or treatment of infectious diseases caused by Clostridioides difficile is on the rise. Thus, in the present invention, a study was conducted on lactic acid bacteria that effectively improves the infectious disease caused by Clostridioides difficile.
이에, 본 발명자들은 클로스트리디오이데스 디피실레(Clostridioides difficile)에 항균 활성을 나타내는 균주를 찾고자 노력한 결과, 클로스트리디오이데스 디피실레에 항균 활성을 갖는 락토바실러스 파라카세이(Lactobacillus paracasei)를 분리, 동정하여 본 발명을 완성하게 되었다.Accordingly, the present inventors tried to find a strain that exhibits antibacterial activity against Clostridioides difficile , as a result of which, as a result of isolating and identifying Lactobacillus paracasei having antibacterial activity against Clostridioides difficile The present invention has been completed.
따라서 본 발명의 목적은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물, 이의 추출물 또는 이로부터 생산되는 박테리오신을 유효성분으로 포함하는 클로스트리디오이데스 디피실레에 대한 항균용 조성물을 제공하는 것이다.Accordingly, an object of the present invention is to provide an antimicrobial composition for Clostridioides difficile comprising Lactobacillus paracasei WiKim0110, a culture thereof, a lysate thereof, an extract thereof, or a bacteriocin produced therefrom as an active ingredient.
본 발명의 다른 목적은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 유효성분으로 포함하는 클로스트리디오이데스 디피실레에 의한 감염 질환의 예방 또는 치료용 약학 조성물을 제공하는 것이다.Another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of infectious diseases caused by Clostridioides difficile comprising Lactobacillus paracasei WiKim0110, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.
또한 본 발명의 다른 목적은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 유효성분으로 포함하는 클로스트리디오이데스 디피실레에 의한 감염 질환의 예방 또는 개선용 식품 조성물을 제공하는 것이다.In addition, another object of the present invention is to provide a food composition for preventing or improving infectious diseases caused by Clostridioides difficile comprising Lactobacillus paracasei WiKim0110, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.
또한 본 발명의 다른 목적은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 유효성분으로 포함하는 발효 스타터를 제공하는 것이다.In addition, another object of the present invention is to provide a fermentation starter comprising Lactobacillus paracasei WiKim0110, its culture, its lysate or its extract as an active ingredient.
또한 본 발명의 다른 목적은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 유효성분으로 포함하는 사료첨가제 또는 사료 조성물을 제공하는 것이다.In addition, another object of the present invention is to provide a feed additive or feed composition comprising Lactobacillus paracasei WiKim0110, its culture, its lysate or its extract as an active ingredient.
또한 본 발명의 다른 목적은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 유효성분으로 포함하는 프로바이오틱스 조성물을 제공하는 것이다.Another object of the present invention is to provide a probiotic composition comprising Lactobacillus paracasei WiKim0110, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.
상기와 같은 본 발명의 목적을 달성하기 위해서, 본 발명은 락토바실러스 파라카세이 WiKim0110(Lactobacillus paracasei WiKim0110)을 제공한다.In order to achieve the object of the present invention as described above, the present invention provides a Lactobacillus paracasei WiKim0110 ( Lactobacillus paracasei WiKim0110).
본 발명에 따른 락토바실러스 파라카세이 WiKim0110(Lactobacillus paracasei WiKim0110)은 유아의 분변 유래의 락토바실러스 파라카세이 균주이다. 비록 본 발명에서의 락토바실러스 파라카세이 WiKim0110을 유아의 분변에서 분리, 동정하기는 했으나, 이의 입수 경로가 이에 한정되는 것은 아니다. The Lactobacillus paracasei WiKim0110 according to the present invention is a Lactobacillus paracasei strain derived from infant feces. Although the Lactobacillus paracasei WiKim0110 in the present invention was isolated and identified from the feces of infants, the route of obtaining it is not limited thereto.
본 발명에의 실시예를 통해 분리된 유아의 분변 유래 유산균 균주는 프로바이오틱스로서 우수하며, 유해 병원균에 대해 우수한 항균 효과를 나타냄을 확인하였다. 또한, 미생물의 동정 및 분류를 위한 16S rRNA 유전자 염기서열 분석 결과, SEQ ID NO: 1의 핵산서열을 갖는 것으로 나타났다. 또한, 분석 결과 상기 미생물은 Lactobacillus paracasei 아종 균주들과 가장 높은 분자계통학적 유연 관계를 보였다.It was confirmed that the lactobacillus strain derived from infant feces isolated through the examples of the present invention is excellent as probiotics and exhibits excellent antibacterial effects against harmful pathogens. In addition, 16S rRNA gene sequencing analysis for identification and classification of microorganisms showed that it has the nucleic acid sequence of SEQ ID NO: 1. In addition, as a result of analysis, the microorganism showed the highest molecular phylogenetic relationship with the subspecies Lactobacillus paracasei strains.
따라서, SEQ ID NO: 1의 16S rRNA 유전자 염기서열을 갖는 본 발명의 미생물을 락토바실러스 파라카세이 CBA3611(Lactobacillus paracasei CBA3611)로 명명하였으며, 국립농업과학원에 2019년 03월 22일자로 기탁하였다 (수탁번호 KACC81092BP). 본 발명에 있어서, 상기 락토바실러스 파라카세이 CBA3611(Lactobacillus paracasei CBA3611)은 락토바실러스 파라카세이 WiKim0110(Lactobacillus paracasei WiKim0110)과 상호교환적으로 사용할 수 있다.Accordingly, the microorganism of the present invention having the 16S rRNA gene sequence of SEQ ID NO: 1 was named Lactobacillus paracasei CBA3611, and was deposited with the National Academy of Agricultural Sciences on March 22, 2019 (accession number KACC81092BP). In the present invention, the Lactobacillus paracasei CBA3611 ( Lactobacillus paracasei CBA3611) can be used interchangeably with the Lactobacillus paracasei WiKim0110 ( Lactobacillus paracasei WiKim0110).
본 발명의 락토바실러스 파라카세이 WiKim0110(Lactobacillus paracasei WiKim0110; 수탁번호 KACC81092BP) 균주는 그람양성균이고 혐기와 호기적 조건에서 생장이 가능한 통성 혐기성(facultative anaerobe)이며, 간균의 형태를 취하고 있다. The strain of Lactobacillus paracasei WiKim0110 (Accession No. KACC81092BP) of the present invention is a Gram-positive bacterium, is a facultative anaerobe that can grow in anaerobic and aerobic conditions, and takes the form of a bacillus.
본 발명에 있어서, '프로바이오틱스(probiotics)'는 사람을 포함한 동물의 위장관 내에서 숙주의 장내 미생물 환경을 개선하여 숙주의 건강에 유익한 영향을 주는 살아있는 미생물'이라는 의미로 이해된다. 프로바이오틱스는 프로바이오틱 활성을 갖는 살아있는 미생물로 단일 또는 복합균주 형태로 사람이나 동물에 건조된 세포 형태나 발효산물 형태로 급여될 경우, 숙주의 장내 균총에 유익한 영향을 미칠 수 있다.In the present invention, "probiotics" are understood to mean "live microorganisms that have a beneficial effect on the health of the host by improving the intestinal microbial environment of the host in the gastrointestinal tract of animals including humans". Probiotics are living microorganisms with probiotic activity, and when fed to humans or animals in the form of single or multiple strains in the form of dried cells or fermented products, they can have a beneficial effect on the intestinal flora of the host.
본 발명의 실시예에서는, 본 발명의 락토바실러스 파라카세이 WiKim0110이 유해 병원균에 대한 항균 테스트에서 높은 항균력을 보이는 것을 확인하였다. 또한, 락토바실러스 파라카세이 WiKim0110의 서열 분석을 통해 상기 WiKim0110이 박테리오신인 엔테로리신 A(enterolysin A) 유전자를 가지고 있는 것을 확인하였다. 본 발명에 따른 락토바실러스 파라카세이 WiKim0110은 프로바이오틱스로서 사람 또는 동물의 유해 병원균의 항균을 위한 용도로 다양하게 사용될 수 있다.In the examples of the present invention, it was confirmed that the Lactobacillus paracasei WiKim0110 of the present invention exhibits high antibacterial activity in an antibacterial test against harmful pathogens. In addition, through sequence analysis of Lactobacillus paracasei WiKim0110, it was confirmed that the WiKim0110 has a bacteriocin, enterolysin A gene. The Lactobacillus paracasei WiKim0110 according to the present invention is a probiotic and can be used in various ways for antibacterial of harmful pathogens in humans or animals.
이에 본 발명의 한 구체예에서는 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 유효성분으로 포함하는 조성물을 제공한다. Accordingly, one embodiment of the present invention provides a composition comprising Lactobacillus paracasei WiKim0110, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.
본 발명에 따른 조성물에 포함되는 락토바실러스 파라카세이 WiKim0110은 사균 또는 생균체로서 존재할 수 있으며, 또한 건조 또는 동결건조된 형태로 존재할 수도 있다. 다양한 조성물 내에 포함시키기 적합한 유산균의 형태 및 제제화 방법은 당업자에게 잘 알려져 있다. Lactobacillus paracasei WiKim0110 included in the composition according to the present invention may exist as dead or live cells, and may also exist in a dried or lyophilized form. Forms of lactic acid bacteria suitable for inclusion in various compositions and methods of formulation are well known to those skilled in the art.
본 발명은 또한 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물, 이의 추출물 또는 이로부터 생산되는 박테리오신을 포함하는 항균용 조성물을 제공한다.The present invention also provides a composition for antibacterial comprising Lactobacillus paracasei WiKim0110, a culture thereof, a lysate thereof, an extract thereof, or a bacteriocin produced therefrom.
한 구체예에서, 상기 항균용 조성물은 클로스트리디오이데스 디피실레에 대한 항균 활성을 갖는 것일 수 있다. 상기 클로스트리디오이데스 디피실레는 설사를 유발하는 대표적인 유해 병원균으로, 장내독소[독소 A(toxin A)], 세포독소 [독소 B(toxin B)] 및 2성분 독소(binary toxin)를 생산하여 설사와 염증 반응을 일으킬 수 있다.In one embodiment, the antimicrobial composition may be one having an antimicrobial activity against Clostridioides difficile. The Clostridioides difficile is a representative harmful pathogen causing diarrhea, and diarrhea by producing intestinal toxin [toxin A], cytotoxin [toxin B], and binary toxin And can cause an inflammatory reaction.
따라서, 본 발명은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 포함하는 유해 병원균에 의한 감염 질환의 예방, 개선 또는 치료용 조성물을 제공한다.Accordingly, the present invention provides a composition for preventing, improving or treating infectious diseases caused by harmful pathogens, including Lactobacillus paracasei WiKim0110, a culture thereof, a lysate thereof, or an extract thereof.
본 발명에 따른 락토바실러스 파라카세이 WiKim0110은 이러한 유리한 작용으로 인해 의약, 건강기능식품, 식품, 사료, 사료첨가제 또는 발효 스타터에 포함될 수 있다.Lactobacillus paracasei WiKim0110 according to the present invention may be included in medicines, health functional foods, foods, feeds, feed additives or fermentation starters due to this advantageous action.
이에, 본 발명은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 유효성분으로 포함하는 클로스트리디오이데스 디피실레에 의한 감염 질환의 예방 또는 치료용 약학 조성물을 제공한다. 본 발명에 있어서, 상기 감염 질환으로는 설사, 독성거대결장, 천공, 패혈증 또는 위막성 대장염일 수 있으나, 이에 제한되는 것은 아니다.Accordingly, the present invention provides a pharmaceutical composition for the prevention or treatment of infectious diseases caused by Clostridioides difficile comprising Lactobacillus paracasei WiKim0110, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient. In the present invention, the infectious disease may be diarrhea, toxic giant colon, perforation, sepsis, or pseudomembranous colitis, but is not limited thereto.
본 발명의 조성물이 약제학적 조성물로 활용될 경우, 본 발명의 약제학적 조성물은 상기 유효성분 이외에 약제학적으로 적합하고 생리학적으로 허용되는 보조제를 사용하여 제조될 수 있으며, 상기 보조제로는 부형제, 붕해제, 감미제, 결합제, 피복제, 팽창제, 윤활제, 활택제 또는 향미제 등을 사용할 수 있다.When the composition of the present invention is used as a pharmaceutical composition, the pharmaceutical composition of the present invention may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant is an excipient, boron Releases, sweeteners, binders, coatings, expanding agents, lubricants, lubricants or flavoring agents may be used.
상기 약제학적 조성물은 투여를 위해서 상기 기재한 유효성분 이외에 추가로 약제학적으로 허용가능한 담체를 1종 이상 포함하여 약제학적 조성물로 바람직하게 제제화할 수 있다.The pharmaceutical composition may be preferably formulated as a pharmaceutical composition, including at least one pharmaceutically acceptable carrier in addition to the active ingredients described above for administration.
예를 들어, 정제 또는 캡슐제의 형태로의 제제화를 위해, 유효성분은 에탄올, 글리세롤, 물 등과 같은 경구, 무독성의 약제학적으로 허용가능한 불활성 담체와 결합될 수 있다. 또한, 원하거나 필요한 경우, 적합한 결합제, 윤활제, 붕해제 및 발색제 또한 혼합물로 포함될 수 있다. 적합한 결합제는 이에 제한되는 것은 아니나, 녹말, 젤라틴, 글루코스 또는 베타-락토오스와 같은 천연당, 옥수수감미제, 아카시아, 트래커캔스 또는 소듐올레이트와 같은 천연 및 합성검, 소듐 스테아레이트, 마그네슘 스테아레이트, 소듐 벤조에이트, 소듐아세테이트, 소듐 클로라이드등을 포함한다. 붕해제는 이에 제한되는 것은 아니나, 녹말, 메틸셀룰로스, 아가, 벤토니트, 잔탄검 등을 포함한다. 액상 용액으로 제제화되는 조성물에 있어서 허용가능한 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충식염수, 알부민 주사 용액, 덱스트로즈 용액, 말토덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders are, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, lacquercanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzo Eate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methylcellulose, agar, bentonite, xanthan gum, and the like. As acceptable pharmaceutical carriers for compositions formulated as liquid solutions, sterilization and biocompatible ones, saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added if necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets.
나아가 해당 분야의 적절한 방법으로 Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA)에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.Further, it may be preferably formulated according to each disease or ingredient using a method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA) as an appropriate method in the field.
또한, 본 발명은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 유효성분으로 포함하는 클로스트리디오이데스 디피실레에 의한 감염 질환의 예방 또는 개선용 식품 조성물일 수 있다.In addition, the present invention may be a food composition for preventing or improving infectious diseases caused by Clostridioides difficile comprising Lactobacillus paracasei WiKim0110, its culture, its lysate or its extract as an active ingredient.
본 발명에 따른 식품 조성물은 상기 약제학적 조성물과 동일한 방식으로 제제화되어 기능성 식품으로 이용하거나, 각종 식품에 첨가할 수 있다. 본 발명의 조성물이 포함되는 식품으로는 예를 들어, 건강기능성 식품, 음료류, 비타민복합제, 건강보조식품류 등이 있다.The food composition according to the present invention may be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods. Foods containing the composition of the present invention include, for example, health functional foods, beverages, vitamin complexes, and health supplement foods.
본 발명의 식품 조성물은 식품 제조시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아추출물 (예를 들어 레바우디오시드A, 글리시르히진 등)] 및 합성향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제와 음료류로 제조되는 경우에는 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 및 각종식물추출액 등을 추가로 포함시킬 수 있다.The food composition of the present invention may include ingredients that are commonly added during food production, and include, for example, proteins, carbohydrates, fats, nutrients, flavoring agents and flavoring agents. Examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)] and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is made of drinks and beverages, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts may be additionally included.
본 발명은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 유효성분으로 포함하는 클로스트리디오이데스 디피실레에 항균 활성을 갖는 조성물을 제공한다.The present invention provides a composition having antibacterial activity against Clostridioides difficile comprising Lactobacillus paracasei WiKim0110, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.
한 구체예에서, 상기 조성물은 생균으로 존재하는 락토바실러스 파라카세이 WiKim0110 균주를 포함하는 경구 투여용 조성물일 수 있다.In one embodiment, the composition may be a composition for oral administration comprising the Lactobacillus paracasei WiKim0110 strain present as live bacteria.
본 발명에 따른 락토바실러스 파라카세이 WiKim0110은 이러한 유리한 작용으로 인해 의약, 건강기능식품, 식품, 사료, 사료 첨가제 또는 발효 스타터 내에 포함될 수 있다. Lactobacillus paracasei WiKim0110 according to the present invention may be included in medicine, health functional food, food, feed, feed additive or fermentation starter due to this advantageous action.
또한, 상기 균주를 유효성분으로 포함하는 식품 조성물은 발효유 등의 음료를 포함할 수 있다. In addition, the food composition containing the strain as an active ingredient may include a beverage such as fermented milk.
이에, 본 발명은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물로 이루어지는 발효 스타터를 제공한다.Accordingly, the present invention provides a fermentation starter consisting of Lactobacillus paracasei WiKim0110, a culture thereof, a lysate thereof, or an extract thereof.
또한, 본 발명은 락토바실러스 파라카세이 WiKim0110, 이의 배양물, 이의 파쇄물 또는 이의 추출물을 유효성분으로 포함하는 사료첨가제 또는 사료로서 이용될 수 있다. In addition, the present invention can be used as a feed additive or feed containing Lactobacillus paracasei WiKim0110, a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.
사료 첨가제로서 이용될 경우, 상기 조성물은 20 내지 90% 고농축액이거나 분말 또는 과립 형태로 제조될 수 있다. 상기 사료첨가제는 구연산, 후말산, 아디픽산, 젖산, 사과산등의 유기산이나 인산 나트륨, 인산 칼륨, 산성 피로인산염, 폴리인산염(중합인산염) 등의 인산염이나, 폴리페놀, 카테킨, 알파-토코페롤, 로즈마리 추출물, 비타민 C, 녹차 추출물, 감초 추출물, 키토산, 탄닌산, 피틴산 등의 천연 항산화제 중 어느 하나 또는 하나 이상을 추가로 포함할 수 있다. 사료로서 이용될 경우, 상기 조성물은 통상의 사료 형태로 제제화 될 수 있으며, 통상의 사료성분을 함께 포함할 수 있다.When used as a feed additive, the composition may be a high concentration of 20 to 90% or may be prepared in the form of powder or granules. The feed additives are organic acids such as citric acid, humic acid, adipic acid, lactic acid, malic acid, or phosphates such as sodium phosphate, potassium phosphate, acid pyrophosphate, and polyphosphate (polyphosphate), polyphenol, catechin, alpha-tocopherol, rosemary Any one or more of natural antioxidants such as extract, vitamin C, green tea extract, licorice extract, chitosan, tannic acid, and phytic acid may be further included. When used as feed, the composition may be formulated in a conventional feed form, and may include a common feed component.
상기 사료첨가제 및 사료는 곡물, 예를 들면 분쇄 또는 파쇄된 밀, 귀리, 보리, 옥수수 및 쌀; 식물성 단백질 사료, 예를 들면 평지, 콩, 및 해바라기를 주성분으로 하는 사료; 동물성 단백질 사료, 예를 들면 혈분, 육분, 골분 및 생선분; 당분 및 유제품, 예를 들면 각종 분유 및 유장 분말로 이루어지는 건조성분 등을 더 포함할 수 있으며, 이외에도 영양보충제, 소화 및 흡수향상제, 성장촉진제 등을 더 포함할 수 있다.The feed additives and feed include grains, such as crushed or crushed wheat, oats, barley, corn and rice; Vegetable protein feeds such as feeds based on rape, soybeans, and sunflowers; Animal protein feeds such as blood meal, meat meal, bone meal and fish meal; It may further include a dry component composed of sugar and dairy products, for example, various milk powders and whey powder, and may further include nutritional supplements, digestion and absorption enhancers, growth accelerators, and the like.
상기 사료첨가제는 동물에게 단독으로 투여하거나 식용 담체 중에서 다른 사료첨가제와 조합하여 투여할 수도 있다. 또한, 상기 사료첨가제는 탑드레싱으로서 또는 이들을 동물사료에 직접 혼합하거나 또는 사료와 별도의 경구제형으로 용이하게 동물에게 투여할 수 있다. 상기 사료첨가제를 동물사료와 별도로 투여할 경우, 당해 기술분야에 잘 알려진 바와 같이 약제학적으로 허용가능한 식용 담체와 조합하여, 즉시 방출 또는 서방성 제형으로 제조할 수 있다. 이러한 식용 담체는 고체 또는 액체, 예를 들어 옥수수전분, 락토오스, 수크로오스, 콩플레이크, 땅콩유, 올리브유, 참깨유 및 프로필렌글리콜일 수 있다. 고체 담체가 사용될 경우, 사료첨가제는 정제, 캡슐제, 산제, 트로키제 또는 함당정제 또는 미분산성 형태의 탑 드레싱일 수 있다. 액체 담체가 사용될 경우, 사료첨가제는 젤라틴 연질 캡슐제, 또는 시럽제나 현탁액, 에멀젼제, 또는 용액제의 제형일 수 있다. The feed additive may be administered to the animal alone or may be administered in combination with other feed additives in an edible carrier. In addition, the feed additives may be easily administered to animals as top dressings, directly mixed with animal feeds, or in an oral formulation separate from feed. When the feed additive is administered separately from animal feed, it can be prepared in an immediate release or sustained release formulation by combining it with a pharmaceutically acceptable edible carrier as well known in the art. Such edible carriers may be solid or liquid, such as corn starch, lactose, sucrose, soy flakes, peanut oil, olive oil, sesame oil and propylene glycol. When a solid carrier is used, the feed additive may be a tablet, a capsule, a powder, a troche or a sugar-containing tablet, or a top dressing in a microdispersible form. When a liquid carrier is used, the feed additive may be a gelatin soft capsule, or a formulation of a syrup, suspension, emulsion, or solution.
또한, 상기 사료첨가제 및 사료는 보조제, 예를 들어 보존제, 안정화제, 습윤제 또는 유화제, 용액촉진제 등을 함유할 수 있다. 상기 사료첨가제는 침주, 분무 또는 혼합하여 동물의 사료에 첨가하여 이용될 수 있다.In addition, the feed additive and feed may contain adjuvants, such as preservatives, stabilizers, wetting or emulsifying agents, solution accelerators, and the like. The feed additive may be used by dipping, spraying, or mixing to add to animal feed.
본 발명의 사료첨가제 또는 사료는 포유류, 가금 및 어류를 포함하는 다수의 동물식이에 적용할 수 있다.The feed additive or feed of the present invention can be applied to a number of animal diets, including mammals, poultry and fish.
상기 포유류로서 돼지, 소, 양, 염소, 실험용 설치동물, 및 실험용 설치동물뿐만 아니라, 애완동물(예: 개, 고양이) 등에게 사용할 수 있으며, 상기 가금류로서 닭, 칠면조, 오리, 거위, 꿩, 및 메추라기 등에도 사용할 수 있고, 상기 어류로서 송어 등에 이용될 수 있으나, 이에 한정되는 것은 아니다.As the mammal, pigs, cows, sheep, goats, experimental rodents, and experimental rodents, as well as pets (eg, dogs, cats), etc. can be used, and as the poultry, chickens, turkeys, ducks, geese, pheasants, And it may be used for quail and the like, and may be used for trout as the fish, but is not limited thereto.
본 발명에 따른 조성물에 포함되는 락토바실러스 파라카세이 WiKim0110 균주의 양은 1회를 기준으로 약 106 내지 1012 cfu/g일 수 있으며, 예컨대 107 내지 1011 cfu/g, 108 내지 1010 cfu/g일 수 있다. 균주를 투여할 경우에는 생균 상태로 투여하는 것이 바람직하며, 섭취 전에 사멸시키거나 감쇄(attenuation) 상태로 투여할 수 있다. 또한, 배양 상등액 등을 사용하여 제조할 경우에는 열처리 과정을 통한 멸균화 과정을 추가적으로 거칠 수 있다. 최소의 효능을 가지는데 필요한 균주량 및 일일 섭취 정도는 섭취자의 신체 또는 건강상태에 따라 달라질 수 있으나, 일반적으로 약 106 내지 1012 cfu/g일 수 있으며, 예컨대 107 내지 1011 cfu/g, 108 내지 1010 cfu/g일 수 있다.The amount of the Lactobacillus paracasei WiKim0110 strain contained in the composition according to the present invention may be about 10 6 to 10 12 cfu/g, for example, 10 7 to 10 11 cfu/g, 10 8 to 10 10 cfu. May be /g. In the case of administering the strain, it is preferable to administer it in a viable state, and it may be killed before ingestion or administered in an attenuation state. In addition, in the case of manufacturing using a culture supernatant or the like, a sterilization process through a heat treatment process may be additionally performed. The amount of strain and the degree of daily intake required to have the minimum efficacy may vary depending on the body or health condition of the ingestor, but may generally be about 10 6 to 10 12 cfu/g, such as 10 7 to 10 11 cfu/g , 10 8 to 10 10 cfu/g.
본 발명의 이점 및 특징, 그리고 그것들을 달성하는 방법은 상세하게 후술되어있는 실시예들을 참조하면 명확해질 것이다. 그러나 본 발명은 이하에서 개시되는 실시예들에 한정되는 것이 아니라 서로 다른 다양한 형태로 구현될 것이며, 단지 본 실시예들은 본 발명의 개시가 완전하도록 하고, 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자에게 발명의 범주를 완전하게 알려주기 위해 제공되는 것이며, 본 발명은 청구항의 범주에 의해 정의될 뿐이다.Advantages and features of the present invention, and a method of achieving them will become apparent with reference to embodiments described below in detail. However, the present invention is not limited to the embodiments disclosed below, but will be implemented in a variety of different forms, and only the present embodiments are intended to complete the disclosure of the present invention, and the general knowledge in the technical field to which the present invention belongs It is provided to completely inform the scope of the invention to those who have it, and the invention is only defined by the scope of the claims.
본 발명에 따른 락토바실러스 파라카세이 WiKim0110은 유해 병원균(클로스트리디오이데스 디피실레)에 대해 우수한 항균 활성을 나타내므로, 프로바이오틱스로서 사람 또는 동물의 유해 병원균에 의한 감염 질환의 예방, 개선 또는 치료 등의 용도를 위해 다양하게 활용될 수 있다. 나아가, 발효 스타터로서 유용하게 사용할 수 있다.Since Lactobacillus paracasei WiKim0110 according to the present invention exhibits excellent antibacterial activity against harmful pathogens (Clostridioides difficile), it is used as a probiotic for preventing, improving or treating infectious diseases caused by harmful pathogens of humans or animals. It can be used in various ways for Furthermore, it can be usefully used as a fermentation starter.
도 1은 16S rRNA 유전자 염기서열을 이용한 락토바실러스 파라카세이 WiKim0110(Lactobacillus paracasei WiKim0110) 균주의 분자계통학적 분석 결과를 나타낸 것이다.
도 2는 락토바실러스 파라카세이 WiKim0110 (Lactobacillus paracasei WiKim0110) 균주의 Clostridioides difficile JCM 1296에 대한 항균력을 확인한 결과이다. (A) 대조군, (B) 락토바실러스 파라카세이 WiKim0110 배양액 처리군.Figure 1 shows the molecular phylogenetic analysis results of the Lactobacillus paracasei WiKim0110 ( Lactobacillus paracasei WiKim0110) strain using the 16S rRNA gene sequence.
Figure 2 is a result of confirming the antibacterial activity of the strain of Lactobacillus paracasei WiKim0110 ( Lactobacillus paracasei WiKim0110) against Clostridioides difficile JCM 1296. (A) Control group, (B) Lactobacillus paracasei WiKim0110 culture solution treatment group.
이하, 본 발명을 실시예를 통해 상세히 설명한다. 하기 실시예는 본 발명을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail through examples. The following examples are merely illustrative of the present invention, and the scope of the present invention is not limited to the following examples.
[실시예][Example]
실시예 1: 락토바실러스 파라카세이 균주의 분리 및 동정Example 1: Isolation and identification of Lactobacillus paracasei strain
유아의 분변시료를 PBS(Phosphate-buffered saline)에 현탁하여 MRS 고체배지에 도말한 다음 30℃에서 2일간 배양하였다. 배양 후 얻은 균 단일집락을 루프로 수거하여 MRS broth에 배양하였다. DNA 추출은 QIAamp DNA Mini Kit(QIAgen, Germany)를 사용하여 추출하였다. 추출된 DNA는 1% 아가로스 겔을 이용하여 확인하였으며, 16S rRNA 유전자를 증폭하기 위하여 추출된 genomic DNA를 주형으로 하여 27F(5'-AGAGTTTGATCCTGGCTCAG-3'), 1492R(5'-CTACGGCTACCTTGTTACGA-3') 프라이머(primer)를 이용하여 PCR을 진행하였고, PCR 조건은 denaturation 95℃ 1분, annealing 45℃ 1분, extension 72℃ 1분 30초로 30회 사이클을 수행하였다. 얻어진 PCR 산물은 염기서열 분석기를 이용하여 서열을 분석하였다. 세균의 동정은 EzBioCloud(https://www.ezbiocloud.net/identify) 데이터베이스를 이용하여 해당 균주의 16S rRNA 유전자의 염기서열과 가장 유사도(similarity)가 높은 세균을 검색하는 방법을 통해 수행되었다. Infant fecal samples were suspended in PBS (Phosphate-buffered saline), spread on MRS solid medium, and incubated at 30° C. for 2 days. A single colony of bacteria obtained after cultivation was collected by loop and cultured in MRS broth. DNA extraction was performed using the QIAamp DNA Mini Kit (QIAgen, Germany). The extracted DNA was confirmed using a 1% agarose gel, and using the genomic DNA extracted to amplify the 16S rRNA gene as a template, 27F(5'-AGAGTTTGATCCTGGCTCAG-3'), 1492R(5'-CTACGGCTACCTTGTTACGA-3' ) PCR was performed using a primer, and PCR conditions were performed 30 cycles with denaturation 95°C for 1 minute, annealing 45°C for 1 minute, and extension 72°C for 1 minute and 30 seconds. The obtained PCR product was sequenced using a nucleotide sequence analyzer. Bacterial identification was performed through a method of searching for bacteria with the highest similarity to the nucleotide sequence of the 16S rRNA gene of the strain using the EzBioCloud (https://www.ezbiocloud.net/identify) database.
본 발명의 실시예를 통해 분리된 균주는 미생물의 동정을 위한 16S rRNA 유전자의 염기서열 분석 결과, 상기 균주는 Lactobacillus paracasei subsp. tolerans DSM 20258 균주와 100% 상동성이 확인되었으나(도 1), 해당 균주와의 전체 유전체를 비교하는 Ortho ANI(Average Nucleotide Identity) 수치는 98.3%로서 유전체 상에서 차이가 있는 다른 균주로 확인되었다.The strain isolated through the embodiment of the present invention is a result of nucleotide sequence analysis of the 16S rRNA gene for the identification of microorganisms, the strain is Lactobacillus paracasei subsp. Tolerans DSM 20258 strain and 100% homology was confirmed (FIG. 1 ), but the Ortho ANI (Average Nucleotide Identity) value comparing the entire genome with the corresponding strain was 98.3%, which was confirmed as another strain with a difference in the genome.
이에, 본 발명의 미생물을 락토바실러스 파라카세이 CBA3611(Lactobacillus paracasei CBA3611)으로 명명하였으며, 국립농업과학원에 2019년 03월 22일자로 기탁하였다(수탁번호 KACC81092BP).Accordingly, the microorganism of the present invention was named Lactobacillus paracasei CBA3611, and was deposited with the National Academy of Agricultural Sciences on March 22, 2019 (accession number KACC81092BP).
실시예 2: 락토바실러스 파라카세이 WiKim0110의 항균 활성 확인Example 2: Confirmation of antibacterial activity of Lactobacillus paracasei WiKim0110
상기 실시예 1을 통해 분리한 락토바실러스 파라카세이 WiKim0110의 단일 콜로니를 MRS 액체배지에 접종하여 30℃ 배양기에서 48시간 배양하였다. 원심분리를 통해 균주와 상층액을 분리하였고, 상층액을 0.2㎕ pore size 필터를 사용하여 세균이 완전히 제거된 균주 배양액을 준비하였다. 배양액은 진공농축기를 사용하여 5배 농축하였다.A single colony of Lactobacillus paracasei WiKim0110 isolated through Example 1 was inoculated in MRS liquid medium and cultured in an incubator at 30° C. for 48 hours. The strain and the supernatant were separated by centrifugation, and the supernatant was prepared with a strain culture solution from which bacteria were completely removed using a 0.2 μl pore size filter. The culture solution was concentrated 5 times using a vacuum concentrator.
상기 락토바실러스 파라카세이 WiKim0110의 항균 활성을 확인하기 위해, 유해 병원균으로 클로스트리이오이데스 디피실레(Clostridioides difficile) JCM 1296을 준비하였다. 상기 유해 병원균을 CDC 배지(BD BBL™ CDC Anaerobe 5%, Sheep Blood Agar - Becton Dickinson)에 도말하고, 종이 디스크를 유해 병원균이 도말된 배지 위에 접종하였다. 농축한 락토바실러스 파라카세이 WiKim0110 배양액 90㎕를 종이디스크에 흡수시켰고, 24시간 후 유해 병원균의 배양 및 락토바실러스 파라카세이 WiKim0110에 의한 배양억제 여부를 확인하였다(도 2). 이때 도 2의 (A)는 락토바실러스 파라카세이 WiKim0110의 배양액을 처리하지 않은 대조군의 결과이며, (B)는 락토바실러스 파라카세이 WiKim0110의 배양액을 처리한 실험군의 결과이다.To confirm the antimicrobial activity of the Lactobacillus paracasei WiKim0110, Clostridioides difficile JCM 1296 was prepared as a harmful pathogen. The harmful pathogens were smeared on a CDC medium (BD BBL™ CDC Anaerobe 5%, Sheep Blood Agar-Becton Dickinson), and a paper disc was inoculated on the medium smeared with harmful pathogens. 90 µl of the concentrated Lactobacillus paracasei WiKim0110 culture solution was absorbed into a paper disc, and after 24 hours, the culture of harmful pathogens and the culture inhibition by Lactobacillus paracasei WiKim0110 were confirmed (FIG. 2 ). At this time, Figure 2 (A) is the result of the control group not treated with the culture medium of Lactobacillus paracasei WiKim0110, (B) is the result of the experimental group treated with the culture medium of Lactobacillus paracasei WiKim0110.
그 결과, 도 2에서 보는 것과 같이, 락토바실러스 파라카세이 WiKim0110 배양액을 처리한 군의 종이디스크에서 클로스트리디오이데스 디피실레 배양 억제 효과가 나타나는 것을 확인하였다.As a result, as shown in Figure 2, it was confirmed that the effect of inhibiting the culture of Clostridioides difficile appears in the paper disc of the group treated with the Lactobacillus paracasei WiKim0110 culture solution.
그 결과, 클로스트리디오이데스 디피실레에 대한 성장 억제 능력을 가짐을 확인하였다(도 2).As a result, it was confirmed that it has the ability to inhibit growth against Clostridioides difficile (FIG. 2).
실시예 3: 락토바실러스 파라카세이 WiKim0110의 박테리오신 유전체 분석Example 3: Analysis of the bacteriocin genome of Lactobacillus paracasei WiKim0110
상기 락토바실러스 파라카세이 WiKim0110의 유전체 분석을 위해 추출된 DNA를 PacBio RS II(Pacific Biosciences)를 이용하여 시퀀싱하고 유전자를 분석하였다. For the genome analysis of the Lactobacillus paracasei WiKim0110, the extracted DNA was sequenced using PacBio RS II (Pacific Biosciences), and the gene was analyzed.
특히, 락토바실러스 파라카세이 WiKim0110의 유전체의 박테리오신 여부는 BAGEL4 webserver(http://bagel4.molgenrug.nl)를 통해 탐색 결과 class Ⅲ에 해당되는 엔테로리신 A(enterolysin A) 유전자를 확인하였다. 엔테로리신 A는 세포벽에 있는 N-아세틸뮤라모일(N-acetylmuramoyl) 잔기와 L-아미노산(L-amino acid) 잔기를 자르면서 세포를 터트려 사멸시키는 광범위한 생장저해 스펙트럼을 갖는 박테리오신으로 확인하였다. Particularly, as a result of searching through the BAGEL4 webserver (http://bagel4.molgenrug.nl), whether or not the genome of Lactobacillus paracasei WiKim0110 is bacteriocin, the enterorlysin A gene corresponding to class III was identified. Enterolysin A was identified as a bacteriocin with a broad spectrum of growth inhibition that bursts and kills cells while cutting N-acetylmuramoyl and L-amino acid residues on the cell wall.
<SEQ ID NO: 2> 엔테로리신 A의 아미노산 서열<SEQ ID NO: 2> Amino acid sequence of enterolysin A
MSYTNKAGANGSSVANRYHDVGASGARANAAYKNNAAAYTAVVGDGGVYVGGYVWGAGTVANANSVGHTSDTKKDYAVYARDMAARYGTSDAGGAGTGKSHWVTHWGDHTDYGYARWGTKKAADANGTTTVDASKSAAASARAVTRNVNVAYGHGRWDVTNGSGDNGAGMNYHDYKVDHGSVKYRVHTVSGWWVAKGDRNDTVNGCAGNAGVDGVTAGSYKAYYRSTTRAGWGVVCDDGTSYTDTYAGGDRGSSNMSYTNKAGANGSSVANRYHDVGASGARANAAYKNNAAAYTAVVGDGGVYVGGYVWGAGTVANANSVGHTSDTKKDYAVYARDMAARYGTSDAGGAGTGKSHWVTHWGDHTDYGYARWGTKKAADANGTTTVDASKSAAASARAVTRNVNVAYGHGRWDVTNGSGDNGAGMNYHDYKVDHGSVKYRVHTVSGWWVAKGDRNDTVNGCAGNAGVDGVTAGSYKAYYRSTTRAGWGVVCDDGTSYTDTYAGGDRGSSN
<110> Korea Food Research Institute <120> LACTOBACILLUS PARACASEI WIKIM0110 HAVING ANTIBACTERIAL ACTIVITY AGAINST CLOSTRIDIOIDES DIFFICILE AND COMPOSITION COMPRISING THE SAME <130> P19R10C0364 <160> 4 <170> KoPatentIn 3.0 <210> 1 <211> 1570 <212> RNA <213> Unknown <220> <223> Lactobacillus sp. Wikim0110 <220> <221> gene <222> (1)..(1570) <400> 1 ttatatgaga gtttgatcct ggctcaggat gaacgctggc ggcgtgccta atacatgcaa 60 gtcgaacgag ttctcgttga tgatcggtgc ttgcaccgag attcaacatg gaacgagtgg 120 cggacgggtg agtaacacgt gggtaacctg cccttaagtg ggggataaca tttggaaaca 180 gatgctaata ccgcatagat ccaagaaccg catggttctt ggctgaaaga tggcgtaagc 240 tatcgctttt ggatggaccc gcggcgtatt agctagttgg tgaggtaatg gctcaccaag 300 gcgatgatac gtagccgaac tgagaggttg atcggccaca ttgggactga gacacggccc 360 aaactcctac gggaggcagc agtagggaat cttccacaat ggacgcaagt ctgatggagc 420 aacgccgcgt gagtgaagaa ggctttcggg tcgtaaaact ctgttgttgg agaagaatgg 480 tcggcagagt aactgttgtc ggcgtgacgg tatccaacca gaaagccacg gctaactacg 540 tgccagcagc cgcggtaata cgtaggtggc aagcgttatc cggatttatt gggcgtaaag 600 cgagcgcagg cggtttttta agtctgatgt gaaagccctc ggcttaaccg aggaagcgca 660 tcggaaactg ggaaacttga gtgcagaaga ggacagtgga actccatgtg tagcggtgaa 720 atgcgtagat atatggaaga acaccagtgg cgaaggcggc tgtctggtct gtaactgacg 780 ctgaggctcg aaagcatggg tagcgaacag gattagatac cctggtagtc catgccgtaa 840 acgatgaatg ctaggtgttg gagggtttcc gcccttcagt gccgcagcta acgcattaag 900 cattccgcct ggggagtacg accgcaaggt tgaaactcaa aggaattgac gggggcccgc 960 acaagcggtg gagcatgtgg tttaattcga agcaacgcga agaaccttac caggtcttga 1020 catcttttga tcacctgaga gatcaggttt ccccttcggg ggcaaaatga caggtggtgc 1080 atggttgtcg tcagctcgtg tcgtgagatg ttgggttaag tcccgcaacg agcgcaaccc 1140 ttatgactag ttgccagcat ttagttgggc actctagtaa gactgccggt gacaaaccgg 1200 aggaaggtgg ggatgacgtc aaatcatcat gccccttatg acctgggcta cacacgtgct 1260 acaatggatg gtacaacgag ttgcgagacc gcgaggtcaa gctaatctct taaagccatt 1320 ctcagttcgg actgtaggct gcaactcgcc tacacgaagt cggaatcgct agtaatcgcg 1380 gatcagcacg ccgcggtgaa tacgttcccg ggccttgtac acaccgcccg tcacaccatg 1440 agagtttgta acacccgaag ccggtggcgt aaccctttta gggagcgagc cgtctaaggt 1500 gggacaaatg attagggtga agtcgtaaca aggtagccgt aggagaacct gcggctggat 1560 cacctccttt 1570 <210> 2 <211> 255 <212> PRT <213> Unknown <220> <223> Enterolysin A <400> 2 Met Ser Tyr Thr Asn Lys Ala Gly Ala Asn Gly Ser Ser Val Ala Asn 1 5 10 15 Arg Tyr His Asp Val Gly Ala Ser Gly Ala Arg Ala Asn Ala Ala Tyr 20 25 30 Lys Asn Asn Ala Ala Ala Tyr Thr Ala Val Val Gly Asp Gly Gly Val 35 40 45 Tyr Val Gly Gly Tyr Val Trp Gly Ala Gly Thr Val Ala Asn Ala Asn 50 55 60 Ser Val Gly His Thr Ser Asp Thr Lys Lys Asp Tyr Ala Val Tyr Ala 65 70 75 80 Arg Asp Met Ala Ala Arg Tyr Gly Thr Ser Asp Ala Gly Gly Ala Gly 85 90 95 Thr Gly Lys Ser His Trp Val Thr His Trp Gly Asp His Thr Asp Tyr 100 105 110 Gly Tyr Ala Arg Trp Gly Thr Lys Lys Ala Ala Asp Ala Asn Gly Thr 115 120 125 Thr Thr Val Asp Ala Ser Lys Ser Ala Ala Ala Ser Ala Arg Ala Val 130 135 140 Thr Arg Asn Val Asn Val Ala Tyr Gly His Gly Arg Trp Asp Val Thr 145 150 155 160 Asn Gly Ser Gly Asp Asn Gly Ala Gly Met Asn Tyr His Asp Tyr Lys 165 170 175 Val Asp His Gly Ser Val Lys Tyr Arg Val His Thr Val Ser Gly Trp 180 185 190 Trp Val Ala Lys Gly Asp Arg Asn Asp Thr Val Asn Gly Cys Ala Gly 195 200 205 Asn Ala Gly Val Asp Gly Val Thr Ala Gly Ser Tyr Lys Ala Tyr Tyr 210 215 220 Arg Ser Thr Thr Arg Ala Gly Trp Gly Val Val Cys Asp Asp Gly Thr 225 230 235 240 Ser Tyr Thr Asp Thr Tyr Ala Gly Gly Asp Arg Gly Ser Ser Asn 245 250 255 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward primer <220> <221> gene <222> (1)..(20) <223> 27F <400> 3 agagtttgat cctggctcag 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Reverse primer <220> <221> gene <222> (1)..(20) <223> 1492R <400> 4 ctacggctac cttgttacga 20 <110> Korea Food Research Institute <120> LACTOBACILLUS PARACASEI WIKIM0110 HAVING ANTIBACTERIAL ACTIVITY AGAINST CLOSTRIDIOIDES DIFFICILE AND COMPOSITION COMPRISING THE SAME <130> P19R10C0364 <160> 4 <170> KoPatentIn 3.0 <210> 1 <211> 1570 <212> RNA <213> Unknown <220> <223> Lactobacillus sp. Wikim0110 <220> <221> gene <222> (1)..(1570) <400> 1 ttatatgaga gtttgatcct ggctcaggat gaacgctggc ggcgtgccta atacatgcaa 60 gtcgaacgag ttctcgttga tgatcggtgc ttgcaccgag attcaacatg gaacgagtgg 120 cggacgggtg agtaacacgt gggtaacctg cccttaagtg ggggataaca tttggaaaca 180 gatgctaata ccgcatagat ccaagaaccg catggttctt ggctgaaaga tggcgtaagc 240 tatcgctttt ggatggaccc gcggcgtatt agctagttgg tgaggtaatg gctcaccaag 300 gcgatgatac gtagccgaac tgagaggttg atcggccaca ttgggactga gacacggccc 360 aaactcctac gggaggcagc agtagggaat cttccacaat ggacgcaagt ctgatggagc 420 aacgccgcgt gagtgaagaa ggctttcggg tcgtaaaact ctgttgttgg agaagaatgg 480 tcggcagagt aactgttgtc ggcgtgacgg tatccaacca gaaagccacg gctaactacg 540 tgccagcagc cgcggtaata cgtaggtggc aagcgttatc cggatttatt gggcgtaaag 600 cgagcgcagg cggtttttta agtctgatgt gaaagccctc ggcttaaccg aggaagcgca 660 tcggaaactg ggaaacttga gtgcagaaga ggacagtgga actccatgtg tagcggtgaa 720 atgcgtagat atatggaaga acaccagtgg cgaaggcggc tgtctggtct gtaactgacg 780 ctgaggctcg aaagcatggg tagcgaacag gattagatac cctggtagtc catgccgtaa 840 acgatgaatg ctaggtgttg gagggtttcc gcccttcagt gccgcagcta acgcattaag 900 cattccgcct ggggagtacg accgcaaggt tgaaactcaa aggaattgac gggggcccgc 960 acaagcggtg gagcatgtgg tttaattcga agcaacgcga agaaccttac caggtcttga 1020 catcttttga tcacctgaga gatcaggttt ccccttcggg ggcaaaatga caggtggtgc 1080 atggttgtcg tcagctcgtg tcgtgagatg ttgggttaag tcccgcaacg agcgcaaccc 1140 ttatgactag ttgccagcat ttagttgggc actctagtaa gactgccggt gacaaaccgg 1200 aggaaggtgg ggatgacgtc aaatcatcat gccccttatg acctgggcta cacacgtgct 1260 acaatggatg gtacaacgag ttgcgagacc gcgaggtcaa gctaatctct taaagccatt 1320 ctcagttcgg actgtaggct gcaactcgcc tacacgaagt cggaatcgct agtaatcgcg 1380 gatcagcacg ccgcggtgaa tacgttcccg ggccttgtac acaccgcccg tcacaccatg 1440 agagtttgta acacccgaag ccggtggcgt aaccctttta gggagcgagc cgtctaaggt 1500 gggacaaatg attagggtga agtcgtaaca aggtagccgt aggagaacct gcggctggat 1560 cacctccttt 1570 <210> 2 <211> 255 <212> PRT <213> Unknown <220> <223> Enterolysin A <400> 2 Met Ser Tyr Thr Asn Lys Ala Gly Ala Asn Gly Ser Ser Val Ala Asn 1 5 10 15 Arg Tyr His Asp Val Gly Ala Ser Gly Ala Arg Ala Asn Ala Ala Tyr 20 25 30 Lys Asn Asn Ala Ala Ala Tyr Thr Ala Val Val Gly Asp Gly Gly Val 35 40 45 Tyr Val Gly Gly Tyr Val Trp Gly Ala Gly Thr Val Ala Asn Ala Asn 50 55 60 Ser Val Gly His Thr Ser Asp Thr Lys Lys Asp Tyr Ala Val Tyr Ala 65 70 75 80 Arg Asp Met Ala Ala Arg Tyr Gly Thr Ser Asp Ala Gly Gly Ala Gly 85 90 95 Thr Gly Lys Ser His Trp Val Thr His Trp Gly Asp His Thr Asp Tyr 100 105 110 Gly Tyr Ala Arg Trp Gly Thr Lys Lys Ala Ala Asp Ala Asn Gly Thr 115 120 125 Thr Thr Val Asp Ala Ser Lys Ser Ala Ala Ala Ser Ala Arg Ala Val 130 135 140 Thr Arg Asn Val Asn Val Ala Tyr Gly His Gly Arg Trp Asp Val Thr 145 150 155 160 Asn Gly Ser Gly Asp Asn Gly Ala Gly Met Asn Tyr His Asp Tyr Lys 165 170 175 Val Asp His Gly Ser Val Lys Tyr Arg Val His Thr Val Ser Gly Trp 180 185 190 Trp Val Ala Lys Gly Asp Arg Asn Asp Thr Val Asn Gly Cys Ala Gly 195 200 205 Asn Ala Gly Val Asp Gly Val Thr Ala Gly Ser Tyr Lys Ala Tyr Tyr 210 215 220 Arg Ser Thr Thr Arg Ala Gly Trp Gly Val Val Cys Asp Asp Gly Thr 225 230 235 240 Ser Tyr Thr Asp Thr Tyr Ala Gly Gly Asp Arg Gly Ser Ser Asn 245 250 255 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Forward primer <220> <221> gene <222> (1)..(20) <223> 27F <400> 3 agagtttgat cctggctcag 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Reverse primer <220> <221> gene <222> (1)..(20) <223> 1492R <400> 4 ctacggctac cttgttacga 20
Claims (9)
상기 클로스트리디오이데스 디피실레에 의한 감염 질환은 설사, 독성거대결장, 천공, 패혈증 또는 위막성 대장염에 의한 것인 약학 조성물.The method of claim 2,
The infectious disease caused by Clostridioides difficile is a pharmaceutical composition that is caused by diarrhea, toxic giant colon, perforation, sepsis or pseudomembranous colitis.
상기 클로스트리디오이데스 디피실레에 의한 감염 질환은 설사, 독성거대결장, 천공, 패혈증 또는 위막성 대장염에 의한 것인 식품 조성물.The method of claim 4,
The infectious disease caused by the Clostridioides difficile is diarrhea, toxic giant colon, perforation, sepsis or gastrointestinal colitis.
상기 식품은 건강기능식품인, 식품 조성물.The method of claim 4,
The food is a health functional food, food composition.
A probiotic composition comprising Lactobacillus paracasei WiKim0110 ( Lactobacillus paracasei WiKim0110; accession number KACC81092BP), a culture thereof, a lysate thereof, or an extract thereof as an active ingredient.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20230086639A (en) * | 2021-12-08 | 2023-06-15 | 한국식품연구원 | Novel lactobacillus paracasei subsp. tolerans wikim0148 with potent anti-inflammatory activity and uses thereof |
WO2024128526A1 (en) * | 2022-12-15 | 2024-06-20 | 주식회사 인트론바이오테크놀로지 | Antimicrobial protein cdl2200 having lytic activity to clostridioides difficile |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20150011060A (en) * | 2013-07-22 | 2015-01-30 | 주식회사 미래자원엠엘 | Lactobacillus paracasei ML-7 strain having antimicrobial activity and uses thereof |
KR101609401B1 (en) * | 2008-04-18 | 2016-04-05 | 꽁빠니 자베 다노느 | Novel strain of lactobacillus paracasei subspecies paracasei having antimicrobial and immunomodulatory properties |
WO2017181158A1 (en) * | 2016-04-15 | 2017-10-19 | Baylor College Of Medicine | Probiotic therapies for developmental disorders and other neurological disorders |
US20170312232A1 (en) * | 2014-10-28 | 2017-11-02 | Medlab Ip Pty Ltd | Treatment for depression and depressive disorders |
-
2020
- 2020-02-07 KR KR1020200015053A patent/KR102463809B1/en active IP Right Grant
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101609401B1 (en) * | 2008-04-18 | 2016-04-05 | 꽁빠니 자베 다노느 | Novel strain of lactobacillus paracasei subspecies paracasei having antimicrobial and immunomodulatory properties |
KR20150011060A (en) * | 2013-07-22 | 2015-01-30 | 주식회사 미래자원엠엘 | Lactobacillus paracasei ML-7 strain having antimicrobial activity and uses thereof |
US20170312232A1 (en) * | 2014-10-28 | 2017-11-02 | Medlab Ip Pty Ltd | Treatment for depression and depressive disorders |
WO2017181158A1 (en) * | 2016-04-15 | 2017-10-19 | Baylor College Of Medicine | Probiotic therapies for developmental disorders and other neurological disorders |
Non-Patent Citations (4)
Title |
---|
Brain Research, Vol.1711, pp.202-213(Epub.2019.01.23.) * |
Journal of Applied Microbiology, Vol.119, pp.1672-1682(2015.)* * |
Nutrients, Vol.10, pp.1-13(Epub.2018.07.12.) * |
대변이식과 대변은행. 과학기술정책 통권 216호, 14~15, (2016) |
Cited By (2)
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---|---|---|---|---|
KR20230086639A (en) * | 2021-12-08 | 2023-06-15 | 한국식품연구원 | Novel lactobacillus paracasei subsp. tolerans wikim0148 with potent anti-inflammatory activity and uses thereof |
WO2024128526A1 (en) * | 2022-12-15 | 2024-06-20 | 주식회사 인트론바이오테크놀로지 | Antimicrobial protein cdl2200 having lytic activity to clostridioides difficile |
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