Karen Nickel, University of Victoria

Karen Nickel (University of Victoria), Rachel Witt (University of Victoria), Mariya Goncheva (University of Victoria)

Building & Escaping

Influenza A virus (IAV) infections are often exacerbated by bacterial co-infection, with Staphylococcus aureus being the most common isolate and a major driver of increased morbidity and mortality. We have found that IAV-S. aureus co-infection enhances viral replication, and specifically that the bacterium's secreted lipases, lipase 1 and lipase 2, are key mediators of this pro-viral effect. We hypothesize that these enzymes promote viral growth by remodeling host cell lipids. To test this, we infected chicken embryo fibroblasts with IAV, treated the cells with recombinant lipase 1 or 2, and performed untargeted lipidomics. This analysis revealed significant changes in the relative abundance of host glycerophospholipids, including phosphatidylcholines and phosphatidylinositols (PI). Supplementing cells with exogenous PI before and after infection with IAV promoted viral replication and partially reproduced the lipase-dependent phenotype. Furthermore, treating cells with PI prior to infection and adding lipase after infection had a synergistic effect on viral growth. Ongoing work is studying how elevated PI supports IAV replication by mapping its effects across the viral life cycle, including entry, genome replication, and virion assembly. We are also testing whether PI-dependent changes in membrane trafficking and lipid signalling pathways contribute to this pro-viral effect. Collectively, these findings reveal a lipid-based mechanism by which S. aureus amplifies IAV infection and identify host PI metabolism as a potential therapeutic target during co-infection.