CA-MRSA strains express the secreted pore-forming leukotoxin Panton-Valentine leukocidin (PVL), however its role in pathogenesis remains controversial. PVL is highly cytotoxic to human macrophages. To gain a more dynamic view how PVL kills, we followed the interaction of PVL with macrophages using live-cell imaging. We are now using genetic approaches to delineate the host death signalling pathways and to determine their role in PVL-positive MRSA infections.