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Faculty of Graduate Studies

Rachel Witt

  • BSc (University of Victoria, 2023)
Notice of the Final Oral Examination for the Degree of Master of Science

Topic

Investigating the pro-viral activity of Staphylococcus aureus lipases on influenza A virus infections

Department of Biochemistry and Microbiology

Date & location

  • Thursday, September 25, 2025
  • 10:30 A.M.
  • Engineering & Computer Science Building, Room 128

Examining Committee

Supervisory Committee

  • Dr. Mariya Goncheva, Department of Biochemistry and Microbiology, University of Victoria (Supervisor)
  • Dr. Caroline Cameron, Department of Biochemistry and Microbiology, UVic (Member)
  • Dr. Leigh Anne Swayne, School of Medical Sciences, UVic (Outside Member)

External Examiner

  • Dr. Lauren Davey, Department of Biochemistry and Microbiology, UVic

Chair of Oral Examination

  • Dr. Scott Watson, Department of Political Science, UVic

Abstract

Influenza A virus (IAV) is the causative agent of the seasonal flu and of severe influenza pandemics in humans. A serious complication of IAV infections is secondary bacterial infection, which can result in bacterial pneumonia and increased mortality. Staphylococcus aureus is the 2nd most common bacterium found in co-infection with IAV, and has been shown to enhance viral infectivity. Lipase 1 is an enzyme secreted by S. aureus, and treatment with it during infection increases the proportion of infectious IAV particles by up to 10-fold in primary fibroblast cells. While the mechanism of this effect is currently unknown, we hypothesise that Staphylococcus aureus lipases modulate select host lipids involved in the budding of influenza A virus virions, resulting in enhanced viral infectivity. Our focus in these experiments is to better understand how this pro-viral effect is being conveyed, and what modifications the lipases are making during an infection. We worked with infections in primary fibroblast cells, and first determined that both S. aureus lipase 1 and lipase 2 are capable of producing the pro-viral effect, and that the effects of the two lipases are not additive. Next, we assessed whether a single exposure to lipase resulted in sustained pro-viral activity in subsequent infections, and found that the lipases do not provide an inheritable benefit to future virions. To look more closely at the molecular changes involved, we used untargeted lipidomics to look for modifications in the host Chicken Embryo Fibroblast (CEF) cell lipidome when exposed to S. aureus lipases during an IAV infection. Through this we identified 20 lipids that were significantly modulated in the lipase-treated samples. The results of the lipidomics were used to inform lipid-treatment infections, where exogenous lipids were added to infections without the presence of lipase. There, we found that treatment with phosphatidylinositol may provide a pro-viral effect similar to the lipases. Together, these experiments give new insight into the mechanisms of the pro-viral activity of S. aureus lipases during co-infection, and could help drive future IAV research and treatments.

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