Grant: Operating Grant

Protein secretion systems play a pivotal role in bacterial pathogenesis and interspecies interactions. Many human pathogens employ the type 6 secretion system (T6SS) to deliver toxic protein effectors to target cells. Aeromonas hydrophila is a ubiquitous waterborne bacterium that can cause severe septicemia and necrotizing fasciitis (flesh-eating disease) in humans, and is recognized as an emerging pathogen by Health Canada. Previous reports showed that T6SS is important for virulence of A. hydrophila but the mechanism is not fully understood. My preliminary data show that A. hydrophila employs its T6SS to kill other bacterial species, suggesting the delivery of antimicrobial effectors. I hypothesize that T6SS is important for the virulence of A. hydrophila by delivering both antimicrobial and anti-eukaryotic effectors. The antimicrobial property of T6SS may allow A. hydrophila to compete with commensal microbiota during infection in the host. I have identified a new T6SS effector that targets bacterial membranes. I expect to exhaustively identify all T6SS effectors in A. hydrophila using a set of advanced tools including highly sensitive mass spectrometry, and next-generation sequencing powered techniques. I will then test the importance of these effectors in virulence using a mouse model. Identification of these effectors will reveal new T6SS functions in A. hydrophila and enhance our understanding of the role of T6SS in pathogenesis.