CONTROL OF CARBOHYDRATE UTILIZATION IN THE PROMINENT GUT BACTERIUM BACTEROIDES THETAIOTAOMICRON

PROJECT SUMMARYThis proposal examines the microbial responses to nutrients by investigating Bacteroidesthetaiotaomicron, a prominent gut commensal bacterium that can grow on a large number ofcarbohydrates that humans and many other microbes cannot utilize. ~18% of the B.thetaiotaomicron's genome is predicted to mediate carbohydrate uptake and breakdown, and theregulation of these processes. This proposal seeks to identify the signals controlling fourregulators of carbohydrate utilization, to define their regulated targets, and to establish how theseproteins exert their regulatory actions. First, we will investigate the control of and by a masterregulator of carbohydrate utilization implicated in gut colonization in several Bacteroides species.This aim also explores the role of a paralog of elongation factor EF-G that is under control of themaster regulator, and like the master regulator, it is necessary for gut colonization andcarbohydrate utilization. Second, we will examine how glucose, the preferred carbon source inmost organisms, silences expression of a transcriptional activator necessary for gut colonizationin a diet-dependent manner. And third, we will determine how the essential transcriptiontermination factor Rho, which harbors a prion-like domain-containing element in B.thetaiotaomicron, adopts different forms and controls different sets of genes required for gutcolonization and carbohydrate utilization. Our studies will reveal the mechanisms andhierarchies governing carbohydrate utilization, and elucidate the role of both of a prion-likedomain in bacterial gene regulation. The proposed investigations may prove paradigmaticbecause they focus on atypical regulatory proteins. In addition, they may help explain whatmakes B. thetaiotaomicron a successful gut colonizer, and its abundance in lean healthyindividuals.