Molecular signatures required for type VIIb secretion system substrate export

Abstract

Most bacteria live in densely colonized environments and are in constant competition for space and nutrients. The result of this competition is an ‘arms race’ in which various strategies for bacterial inhibition have evolved, such as the bacterial type VII secretion system (T7SS), directly inject toxins into competitor bacteria. The T7SS is a macromolecular machine unique to the Gram-positive phyla Actinobacteria and Firmicutes and is further divided into genetically distinct subtypes denoted T7SSa and T7SSb, respectively. The T7SSa is well-characterized in Mycobacteria, however, the T7SSb remains understudied. These two systems share a conserved membrane-embedded ATPase and the secretion of small α-helical proteins (called “effectors”), some of which are toxic and drive bacterial pathogenicity by facilitating microbe-microbe and host-microbe interactions. My graduate thesis seeks to determine the secretion mechanism of T7SSb effectors in the genus Streptococcus. This includes characterization of chaperones that directly interact with the effectors and mediate their export. Insights from understanding the molecular signatures that dictate effector export will help determine the apparatus component that recognizes these signatures and facilitates effector transport through the apparatus. This will provide significant inroads into understanding the type VIIb secretion mechanism.