Virulence mechanisms of human respiratory pathogens
Pseudomonas aeruginosa and the Anginosus Group of Streptococci are two major groups of bacterial pathogens associated with lung infections in individuals afflicted with the genetic disease cystic fibrosis (CF). Using genetic, biochemical, and structural approaches, we are interested in understanding how the many virulence factors produced by these bacteria contribute to their ability to cause infectious disease.
mechanisms of bacterial Killing by the Type VI secretion system
The bacterial type VI secretion system is a contractile nanomachine used by Gram-negative bacteria to inject antibacterial toxins into neighbouring bacteria. It is used by both commensal and pathogenic bacteria to compete for space and nutrients in numerous contexts including the human gut microbiome. We are interested in understanding how these antibacterial toxins are transported from one cell to another and how they exert toxicity once delivered to a target cell. By understanding the molecular principles underlying this process it is our long term goal to be able to rationally manipulate bacterial populations relevant to human health.
exopolysaccharide secretion and bacterial adhesion
Many species of bacteria exist in dense cellular aggregates held together by bacterially produced exopolysaccharides. In this form, bacteria are difficult to eradicate due in part to decreased efficacy of antibiotics. We are interested in determining how bacterial exopolysaccharides are synthesized and exported from the cell. By understanding how this process occurs at the molecular level, we hope to one day be able to inhibit exopolysaccharide secretion under circumstances where it is detrimental to human activities (i.e. biofouling of pipes, colonization of indwelling medical devices, etc.).
Type VII secretion-dependent Bacterial Antagonism
In contrast to their Gram-negative counterparts, the identification of pathways involved in bacterial antagonism between Gram-positive bacteria has long remained elusive. In recent work, we and others have found that the type VII secretion system exports antibacterial toxins that mediate bacterial competition. Elucidating the mode of action of these toxins will allow for the identification of new vulnerabilities in Gram-positive cells that can be exploited for the development of new antibiotics.