Staphylococcus aureustoxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration

Abstract

ABSTRACTbackgroundStaphylococcus aureusPanton Valentine Leukocidin (PVL) is a pore-forming toxin targeting the human C5a receptor (hC5aR), enabling this pathogen to battle the immune response by destroying phagocytes through targeted lysis. The mechanisms that contribute to rapid cell lysis are largely unexplored.ResultsHere we show that cell lysis may be enabled by a process of toxins targeting receptor clusters and receptor ‘recycling’ which allows multiple toxin pores to be formed close together. Using live cell single-molecule super-resolution imaging, Förster resonance energy transfer (FRET) and nanoscale total internal reflection fluorescence (TIRF) colocalization microscopy we visualized toxin pore formation in the presence of its natural docking ligand.ConclusionsWe demonstrate disassociation of hC5aR from toxin complexes and simultaneous binding of new ligands. This effect may free mobile receptors to amplify hyper inflammatory reactions in early stages of microbial infections and have implications for several other similar bi-component toxins and the design of new antibiotics.