Multiple virulence factors are required for Staphylococcus aureus-induced apoptosis in endothelial cells

Abstract

SummaryStaphylococcus aureus infections can result in sepsis and septic shock associated with vascular damage and multiple organ failure. Apoptosis appears to play a key role during sepsis, and the ability of S. aureus to induce apoptosis in endothelial cells might contribute to metastatic infection. In contrast to leukocytes, in human umbilical vein endothelial cells and two endothelial cell lines neither purified a a a a -toxin nor staphylococcal supernatants were sufficient to induce apoptosis. Apoptosis induction instead required staphylococcal invasion as well as signals from metabolically active intracellular staphylococci. Only strongly haemolytic and invasive staphylococci, but not non-invasive strains induced apoptosis that was caspase-dependent but Fas-independent. However, only a subgroup of clinical isolates with an invasive and haemolytic phenotype induced apoptosis. Expression of a a a a -toxin in a non-haemolytic strain partially restored apoptosis induction, suggesting a role of a a a a -toxin as a trigger of apoptosis. Furthermore, infection of endothelial cells with isogenic mutants of various regulator genes revealed that apoptosis induction was dependent on the global regulator agr and the alternative sigma factor sigB , but not influenced by sarA . Together, our results indicate that the ability of S. aureus to induce apoptosis in endothelial cells is determined by multiple virulence factors.

Technetium 99m–Labeled Annexin V Scintigraphy of Platelet Activation in Vegetations of Experimental Endocarditis

“…This proteolytic activity in the vicinity of the vegetation has 2 consequences: one is to promote lysis of the vegetation itself and dissemination of septic emboli, and another is to promote degradation of the extracellular matrix and invasion of the underlying tissue, leading to valvular damage and/or abscess formation. 47,48 In conclusion, our present study demonstrated that 99m…”

Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation

“…However, rsp mutation neither influences internalization of S. aureus by HeLa cells nor phagosomal escape (SI Appendix, Fig. S2), both of which have been shown to be associated with cytotoxicity (29)(30)(31). Thus, our data suggest that rsp-defective S. aureus remain within the host cell longer and delay pathogen-induced cell death.…”

Role of SCC mec Type in Outcome of Staphylococcus aureus Bacteremia in a Single Medical Center

“…The outcome is usually determined by virulence factors and host response (15,16,18,21,24,36). Many virulence factors have been implicated in invasiveness, disease severity, and persistent bacteremia (1,8,10,11,12,24,30,36). Several studies have shown that methicillin-resistant S. aureus (MRSA) isolates are associated with higher mortality (5,32,33,36).…”