Targeting host factors in infections

Staphylococcus aureus is a human pathogen that causes a wide array of infections. Despite the strong epidemiological association of the pore-forming toxin, Panton-Valentine leukocidin (PVL) with S. aureus pathogenesis, the exact mechanism by which PVL kills host cells such as innate immune cells remains poorly understood. In this thesis, I have used a genome-wide CRISPR screen to identify host factors that promote PVL-mediated killing of macrophages. The screen identified the cell surface receptor C5aR1 which binds PVL, but also FBXO11 and HDAC5. The findings suggest that both, FBXO11 and HDAC5, regulate C5aR1 expression and thus susceptibility to PVL. This raises the potential to use existing compounds as therapeutics against S. aureus infections.