[논문]생물막 분산기작을 이용한 만성창상의 치료전략

김재수; 김민호

doi:10.7845/kjm.2019.9036

[국내논문] 생물막 분산기작을 이용한 만성창상의 치료전략
Therapeutic strategies to manage chronic wounds by using biofilm dispersal mechanisms 원문보기

Korean journal of microbiology = 미생물학회지, v.55 no.2, 2019년, pp.87 - 102

김재수 (경기대학교 바이오융합학부 생명과학전공) , 김민호 (켄트주립대학교 생물학과)

초록
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대부분의 만성창상(chronic wounds)은 생물막으로 인해 상처 치유시 염증단계를 지속시킨다. 생물막은 항생제(antibiotics)에 대한 저항성을 가지며 침투력을 저하시키고 살균제(biocides)에 대한 내성을 지니며 국소면역반응을 약화시킨다. 또한 생물막은 주변의 조직에 단단히 붙어 있어 제거하는 작업이 매우 어렵다. 그러므로 주변 조직을 손상시키지 않으면서 단단한 생물막을 제거하는 전략은 매우 중요하다. 그 중에 하나가 분산기작을 이용한 생물막의 해체이며 지금까지 많은 연구가 수행되어 왔다. 본 고찰논문에서는 특별히 화학주성, 파지요법, 다당류, 다양한 효소(당분해효소, 단백질분해효소, DNA 분해효소), 계면활성제, 분산신호, 자기유도인자, 조절인자, 억제제 등이 소개되었으며 더 나아가 항생제 치료 및 다른 치료와의 병행을 통한 병합요법도 소개되었다. 앞으로 본 논문에서 제시된 생물막의 분산기작의 지식을 이용하여 만성 창상 감염치료의 가능성이 더 높아지길 기대한다.

Abstract ▼ AI-Helper

Most chronic wounds persist in the inflammatory phase during wound healing due to the biofilm. Biofilms are resistant to antibiotics, weakening penetration, resistance to biocides and weakening local immune responses. The biofilm is firmly attached to the surrounding tissues and is very difficult to remove. Therefore, strategies to remove hard biofilms without damaging surrounding tissue are very important. One of possible strategies is dispersal. So many studies have been done to develop new strategies using dispersal mechanisms. In this review paper, especially chemotaxis, phage therapy, polysaccharides, various enzymes (glycosidases, proteases, and deoxyribonucleases), surfactants, dispersion signals, autoinducers, inhibitors were introduced. Combination therapies with other therapies such as antibiotic therapy were also introduced. It is expected that the possibility of treatment of chronic wound infection using the knowledge of the biofilm dispersal mechanisms presented in this paper will be higher.

Keyword

표/그림 (3)

그림 Fig. 1. The life cycle of biofilm.
그림 Fig. 2. The steps of biofilm dispersal.
표 Table 1. List of active dispersal mechanisms that may be useful for wound infection treatments

AI 본문요약
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제안 방법

, 2009). DNase 처리로 Staphylococcus와 Enterococcus의 생물막 형성을 막았고(Guiton et al., 2009; Mann et al., 2009), 실험상에서(in vitro) 이미 형성된 생물막을 분산시켰다(Izano et al., 2008; Guiton et al., 2009). DNase I의 재조합 형태인, pulmozyme은 낭포성섬유증(cystic fibrosis, CF) 환자를 치료하는 특수한 경우에 사용되었다(Shak et al.

성능/효과

, 2008). 펩티드 1037은 매우 약한 항균활성을 나타내지만, 그람음성 병원균인 P. aeruginosa 및 Burkholderia cenocepacia와 그람양성 L. monocytogenes 에 의한 생물막 형성을 효과적으로 방지하여 생물막에서 세포 사멸을 유도할 수 있었다. P.
파지와 효소: 고정상 세포에서 복제하는 dispersin B를 생성하도록 공학적으로 변형한 파지는 시험관 내에서 이미 형성된 E. coli 생물막의 완전한 파괴를 유도했는데 비가공파지 또는 dispersin B 단독 투여보다 더 현저한 효과를 나타냈다. 이는 dispersin B 매개 EPS 분해로 파지가 생물막 구조의 더 깊은 층에 접근하도록 허용했기 때문이다(Lu and Collins, 2007).

후속연구

분산은 생물막 발달의 마지막 단계이며 수많은 환경신호, 신호전달 경로 및 작용기(effectors)가 관여하는 정족수감지기작의 일부로 복잡한 과정이다(Karatan and Watnick, 2009). 지금까지 분산기작이 완전히 이해되지는 않았지만 분산기작에 관련된 많은 연구가 임상적으로 유용한 약제의 개발이나 특별히 만성질환을 위한 방법개발을 선도해 나갈 것으로 기대된다. 생물막 관리를 위한 전략을 개발하기 위해 임상적으로 유용한 세 가지 가능한 분산기작은 (1) 생물막 기질의 파괴, (2) 정족수감지 기작을 통한 생물막 형성 저해, (3) 생물막에서 세포탈출 유도가 있다.
만성창상과 같은 만성질환에서 생물막의 분산은 항생제 요법과 같은 약물치료뿐만 아니라 감염된 박테리아세포가 숙주 방어에 노출됨으로 인해 제어가 쉬워진다. 따라서 분산에 의한 생물막 관리는 향후 치료기술, 특히 만성창상과 같은 만성감염질환에서 유용한 전략이 될 수 있다. 창상치료에 활용 가능할 것으로 추정되는 지금까지 밝혀진 분산기작을 총망라하여 Table 1에 정리하였다.
분산은 창상의 효과적인 치료를 위한 가장 기대되는 분야 중 하나이다. 본 고찰에서 소개된 많은 분산제 또는 신호(cues)들은 창상치료에 적용 가능한 많은 선택 중 하나가 될 수 있고 항 생제요법과 같은 다른 치료법들과 병행하여 다양하게 개발될 수 있다. 그러나 많은 연구에서 어떤 분산전략이 효과적인지 선택하는데 도움을 주기 때문에 메타게노믹스(metagenomics) 를 통한 창상의 생물막에 존재하는 세균의 군집구조를 분석하는 것이 필요할지도 모른다.
거의 모든 분산연구가 실험실의 통제된 조건하에서 즉 시험관 내에서 수행되었기 때문에 이러한 결과를 창상의 생물막과 같은 실제 임상상황에 적용하는 것은 극히 어렵다. 따라서 앞으로의 연구는 많은 연구자와 임상의들이 동물 또는 인간의 창상에서 이미 개발된 다양한 분산전략을 실제 임상에 사용할 것을 강력하게 권장한다. 실용적인 응용을 통한 지속적인 연구는 분산에 대한 많은 이전 연구들의 가치를 높일 것으로 전망된다.

질의응답

핵심어	질문	논문에서 추출한 답변
	생물막을 구성하는 미생물의 종류에는 어떤 것이 있는가?	생물막은 하나 또는 여러 유형의 표면부착 미생물과 그들이 생성한 세포 외 고분자 물질(extracellular polymeric substances, EPS)로 구성된 점액질의 집합체를 일컫는 말이다. 세포 외 고분자물질로는 다당류, 단백질, 지질 및 DNA 등이 있고 생물막을 생성하는 미생물의 종류로는 세균(bacteria), 곰팡이(fungi), 원생생물(protists)이 있다. 생물막은 생물 또는 무생물의 표면 등 여러 종류의 표면에서 자랄 수 있는데 자연, 환경, 산업, 의료 등의 분야에서 발견된다.
	생물막이란 무엇인가?	생물막은 하나 또는 여러 유형의 표면부착 미생물과 그들이 생성한 세포 외 고분자 물질(extracellular polymeric substances, EPS)로 구성된 점액질의 집합체를 일컫는 말이다. 세포 외 고분자물질로는 다당류, 단백질, 지질 및 DNA 등이 있고 생물막을 생성하는 미생물의 종류로는 세균(bacteria), 곰팡이(fungi), 원생생물(protists)이 있다.
	생물막은 생물 또는 무생물의 표면 등 여러 종류의 표면에서 자랄 수 있는데, 대표적인 예로는 어떤 것이 있는가?	생물막은 생물 또는 무생물의 표면 등 여러 종류의 표면에서 자랄 수 있는데 자연, 환경, 산업, 의료 등의 분야에서 발견된다. 가장 대표적인 예로는 치아의 표면에 형성되는 치석(dental plaque)을 들 수 있다. 생물막은 3차원 구조를 가지며 공동체를 이루고 살기 때문에 미생물 도시라고도 표현한다.

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표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

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