dc.description.abstract | Bacterial chemotaxis to microbial-derived metabolites likely plays a key role in shaping the diversity in microbial communities in the gastrointestinal tract (GI tract). Among the important metabolites is indole, which modulates chemotaxis through unknown mechanisms. As indole is produced by the many species in the gut microbiota and as it strongly impacts bacterial physiology, the basis of chemotaxis to indole is of major interest.
In this work, we dissected the mechanisms underlying indole chemotaxis in Escherichia coli. We characterized the role of two major chemoreceptors, Tar and Tsr, in sensing indole. Our findings suggest that Tsr and Tar mediate opposite responses to indole, and that the difference in the kinetics of the responses induces biphasic chemotaxis. Biphasic chemotaxis attracts cells that have previously adapted to the metabolite to indole-rich niches. However, it repels cells that have not adapted to the metabolite from indole-rich niches. This causes a bifurcation of the population of cells based on their chemotaxis response. Based on these observations, we propose that indole maintains gut homeostasis by recruiting beneficial commensal bacteria and repelling pathogenic bacteria. We further characterized the structural domains in Tar and Tsr that are responsible for this biphasic chemotaxis response to indole. We have found that the periplasmic domain of Tsr senses indole as a repellent, contradicting earlier reports. Interestingly, our experiments suggest that indole activates all the major domains of Tar: the periplasmic, the HAMP, and the cytoplasmic. Finally, we have investigated the integrated effect of the indole and another important class of microbial metabolites – short chain fatty acids (SCFA), on chemotaxis. Our findings show that the presence of indole can cause an unexpected inversion from repellent to attractant chemotaxis towards SCFAs. | |