Quorum sensing in the commensal bacterium Bacteroides fragilis Intestinal epithelial cells provide the crucial interface (400 m) 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.
Significance and implications for human health: The intestinal epithelium represents a crucial interface between mammals and their microbial partners, yet little is known about the mechanisms regulating beneficial relations with these commensal bacteria. By investigating quorum sensing in commensal bacteria in the intestine, I hope to uncover mechanisms that will lead to therapeutic manipulation of gut microflora to treat inflammatory bowel disease (IBD), a group of chronic disorders thought to arise through disregulated relationships between host and commensals . Beyond treating IBD patients, a rigorous understanding of commensal bacterial-human gut interactions could lead to strategies to exploit beneficial bacteria, prevent infection by invading microbes, and generally improve human health.