Quorum Sensing in the Commensal Bacterium Bacteroides fragilis

描述(申请人提供)：共生细菌脆弱类杆菌肠道上皮细胞的群体感应提供了哺乳动物宿主和大量微生物伙伴之间的关键界面(400平方米)。然而，人们对调节我们与共生细菌之间的有益关系的机制知之甚少。在一种称为群体感应的过程中，细菌使用称为自体诱导剂的化学信号分子进行交流。群体感应使细菌能够同步集体行为，如多糖分泌和生物膜形成，这是哺乳动物肠道环境中共生细菌部署的标志特征。细菌和哺乳动物肠道细胞不断接触的事实，再加上原核生物和真核生物细胞间通讯的普遍使用，使我推测细菌和/或哺乳动物分泌的信号通过界内和界间通讯参与维持动态平衡。我将通过研究脆弱类杆菌与真核细胞的相互作用来研究这些想法。脆弱芽孢杆菌是肠道正常菌群中的重要成员，通过引导宿主抗炎反应在维持肠道健康方面发挥着至关重要的作用。然而，这些相互作用背后的机制尚不清楚。这项建议的目的是研究肠道细菌如何通过群体感应行为影响肠道健康，表征引导脆弱芽孢杆菌集体行为的群体感知因子，并确定宿主免疫系统如何控制脆弱杆菌群体感知。

DESCRIPTION (provided by applicant): Quorum sensing in the commensal bacterium Bacteroides fragilis Intestinal epithelial cells provide the crucial interface (400 m2) between mammalian hosts and a vast consortium of microbial partners. Yet, little is known about the mechanisms regulating our beneficial relations with commensal bacteria. In a process called quorum sensing, bacteria communicate using chemical signal molecules called autoinducers. Quorum sensing allows bacteria to synchronize collective behaviors such as polysaccharide secretion and biofilm formation, hallmark traits deployed by commensal bacteria in the mammalian gut environment. The fact that bacteria and mammalian intestinal cells are in constant contact with one another, combined with the universal use of intercellular communication in prokaryotes and eukaryotes, has led me to speculate that bacteria- and/or mammalian-secreted signals are involved in maintaining homeostasis via intra- and inter-kingdom communication. I will investigate these ideas by studying Bacteroides fragilis-eukaryotic cell interactions. B. fragilis is a prominent member of the normal gut microflora that plays a vital role in maintaining intestinal health by directing host anti-inflammatory responses. However, the mechanisms underlying these interactions are not known. The goals of this proposal are to investigate how resident gut bacteria influence intestinal health through quorum sensing behaviors, to characterize quorum sensing factors directing collective behaviors in B. fragilis, and to define how the host immune system controls B. fragilis quorum sensing.