深海来源真菌中群感效应抑制剂的发现及其影响铜绿假单胞菌的分子机制研究

Pseudomonas aeruginosa is an opportunistic pathogen commonly found in the environment. It’s known to be highly antibiotic resistant and able to grow in a variety of generally inhospitable environments. Quorum sensing inhibitors (QSIs) have been suggested as a novel approaches for anti-infective therapy. They can inhibit pathogenicity and drug-resistance of pathogens by disturbing quorum sensing of microorganism and inhibiting biofilm formation. However the lacks of enough active compounds and mechanism research limit the application of QSIs. Deep-sea resource will be one of the key areas of concern during thirteen five year plan of China. Currently we gained three stains of deep-sea-derived active fungi from South China Sea sediment. They contained QSIs because their extracts could inhibit biofilm formation of Pseudomonas aeruginosa PAO1. We want to isolate the bioactive QSIs against Pseudomonas aeruginosa PAO1 from the fungi and elucidate their structures. Forth more, we will investigate their activities to biofilm, the influence to motility and virulence of Pseudomonas aeruginosa PAO1. And we are going to illustrate the molecular mechanisms of QSIs against Pseudomonas aeruginosa PAO1. It will be helpful to discover the relationship between QSIs and pathogen. Also it will be meaningful to search new antibiotics agents, and explore South China Sea biological resource.

铜绿假单胞菌是常见的耐药致病菌，防治困难，威胁人类健康。铜绿假单胞菌的致病性、耐药性都跟群感效应密切相关。群感效应抑制剂通过干扰群感效应，进而减少致病菌的耐药性和致病性，是新型抗生素研究的热点之一。但目前群感效应抑制剂活性单体较少，作用机理不明确，限制了其进一步的开发利用。深海资源是我国“十三五”规划重点关注的领域之一。本组从深海微生物资源中，发现多株南海深海来源真菌中含有群感效应抑制剂。本项目将在现有研究基础上，首次研究深海来源真菌中的群感效应抑制剂成分，阐明其化学结构，研究群感效应抑制剂对铜绿假单胞菌致病性和耐药性的体内外影响及其分子机理，以期获得新型的抗铜绿假单胞菌先导化合物。本项目对于研究深海真菌中的群感效应抑制剂结构特点、探讨群感效应抑制剂与致病微生物的关系、研究和开发利用我国深海生物资源、推动国家海洋战略，均具有一定意义。同时，还将为研发新型抗生素提供理论支持和先导化合物。

铜绿假单胞菌、耐甲氧西林金黄色葡萄球菌等致病菌的致病性、耐药性都跟群感效应密切相关。群感效应抑制剂通过干扰群感效应，进而减少致病菌的耐药性和致病性，是新型抗生素研究的热点之一。但目前群感效应抑制剂活性单体较少，作用机理不明确，限制了其进一步的开发利用。项目负责人系统研究了4株深海来源真菌的活性成分，筛选并获得了一批具有抑制生物被膜形成活性的群感效应抑制剂，阐明部分群感效应抑制剂对铜绿假单胞菌、耐甲氧西林金黄色葡萄球菌致病性、毒力因子的作用机制。本项目对于研究深海真菌中的群感效应抑制剂结构特点、探讨群感效应抑制剂与致病微生物的关系、研究和开发利用我国深海生物资源、推动国家海洋战略，均具有一定意义。同时，还将为研发新型抗生素提供理论支持和先导化合物。