Staphylococcus aureus toxins

Abstract

Staphylococcus aureus is a dangerous pathogen that causes a variety of severe diseases. The virulence of S. aureus is defined by a large repertoire of virulence factors, among which secreted toxins play a preeminent role. Many S. aureus toxins damage biological membranes, leading to cell death. In particular, S. aureus produces potent hemolysins and leukotoxins. Among the latter, some were recently identified to lyse neutrophils after ingestion, representing an especially powerful weapon against bacterial elimination by innate host defense. Furthermore, S. aureus secretes many factors that inhibit the complement cascade or prevent recognition by host defenses. Several further toxins add to this multi-faceted program of S. aureus to evade elimination in the host. This review will give an overview over S. aureus toxins focusing on recent advances in our understanding of how leukotoxins work in receptor-mediated or receptor-independent fashions.

Fig. 1

Membrane-damaging toxins. Alpha-toxin and the bi-component leukotoxins of S. aureus bind to specific receptors, upon which formation of a defined pore occurs. Receptors have been identified for alpha-toxin, PVL, LukAB (LukGH), and LukDE. Probably gamma-toxin also binds to a specific receptor. PSMs are believed to attach to the cytoplasmic membrane in a non-specific fashion and lead to membrane disintegration. Probably the phospholipid composition and membrane charge are important for cell susceptibility to PSMs. Pores formed by PSMs are likely short-lived, as shown for delta-toxin.

Fig. 2

Neutrophil lysis after phagocytosis. Lysis after phagocytosis from within the neutrophil phagosome was demonstrated for S. aureus PSMα peptides and the leukotoxin LukAB (LukGH), illustrated here for PSMs. PSMs trigger neutrophil activation by interaction with the FPR2 receptor. After phagocytosis and phagosome formation, bacterial regulatory systems (Agr, stringent response) lead to PSM production and PSM-mediated phagosome lysis. Bacteria may further proliferate in the neutrophil. Upon ultimate neutrophil destruction the bacteria escape from the cell.