Defining the Bacteroidetes Type VI Secretion System MC-BP Interface and Regulation

ABSTRACT The human gastrointestinal tract is densely colonized by microorganisms which must compete in order to survive. This competition dictates which microorganisms fill dominate roles in the microbiome, and in turn have the strongest influence over host health. The Type VI Secretion System (T6SS) is a mechanism utilized by Gram-negative members of the gut microbiota to compete. The T6SS functions by injecting toxic effectors in a contact-dependent manner into recipient cells, resulting in target cell death and proliferation of attackers. T6SS are employed by pathogenic invaders of the gut, such as Vibrio cholerae, as well as bacteria considered healthy commensals. Two major phyla of bacterial residents in the gut employ T6SS, Proteobacteria and Bacteroidetes. The Proteobacteria T6SS, designated T6SSi, has been well-studied over the past decade. T6SSi activity is known to rely on the membrane complex, the transenvelope channel for effector translocation, and the baseplate, the assembly hub and initiator of firing. The Bacteroidetes T6SS, T6SSiii, has been recently reported by our group to encode a novel membrane complex, while retaining a structurally conserved baseplate. How the baseplate could evolve a unique adaptor functionality to interact with a distinct membrane complex is unknown. In addition, nothing is known regarding regulation of T6SSiii assembly, whether in individual cells, a bacterial community, or a colonized mammalian GI tract. This candidate will investigate the membrane complex-baseplate interface in Bacteroides fragilis (Aim 1), a ubiquitous gut Bacteroidetes, as well as the T6SSiii regulation of assembly (Aim 2). Pursuit of these aims will require training in new techniques, mentorship from experts in varied fields, enrichment of collaborative networks, as well as strengthening and expansion of the candidate’s scientific and professional skills. Ultimately, the candidate will receive support in entering the field of academia, and become better equipped to teach and train others in that career path.