Conway, Kate

Project title: Investigating the effects of bacterial-derived antimicrobial peptides on host immunity

Department: Biochemistry and Microbiology

Faculty supervisor: Dr. Lisa Reynolds

"Treponema pallidum is the causative agent of syphilis. It is a motile spirochete bacteria that infects humans through breaches in epithelial cells during sexual contact, disseminates via the blood and lymphatic systems and invades a variety of tissues and organs. The Cameron Laboratory at UVic have recently identified T. pallidum proteins that have microbicidal activity against a range of bacterial species in vitro. Why T. pallidum produces these antimicrobial proteins is unclear, although it seems likely that production of these allows T. pallidum to gain a competitive advantage against other microbes it encounters in the human host.

In addition to direct microbicidal effects, many well-characterized antimicrobial peptides also have modulatory effects on mammalian immune cells. For example, several antimicrobial peptides have been reported to alter inflammatory cytokine production from phagocytic cells or epithelial cells. This raises the hypothesis that T. pallidum produces antimicrobial peptides which have direct modulatory effects on host cytokine production and facilitate its ability to invade and disseminate throughout the host. This project will test this hypothesis by culturing murine and human epithelial and macrophage cell lines with recombinant T. pallidum antimicrobial peptides and examining the resulting host cytokine production using cytometric bead array assays and enzyme-linked immunosorbent assays. Known immunomodulating antimicrobial peptides will be included as a positive control, and T. pallidum proteins lacking antimicrobial activity will be included as a negative control in these assays. It is expected that this project will contribute to fundamental knowledge about how this important human pathogen colonizes host tissue."