The general stress response of Staphylococcus aureus promotes tolerance of antibiotics and survival in whole human blood

Staphylococcus aureus is a frequent cause of invasive human infections such as bacteraemia and infective endocarditis. These infections frequently relapse or become chronic, suggesting that the pathogen has mechanisms to tolerate the twin threats of therapeutic antibiotics and host immunity. The general stress response of S. aureus is regulated by the alternative sigma factor B (aB) and provides protection from multiple stresses including oxidative, acidic and heat. aB also contributes to virulence, intracellular persistence and chronic infection. However, the protective effect of aB on bacterial survival during exposure to antibiotics or host immune defences is poorly characterized. We found that aB promotes the survival of S. aureus exposed to the antibiotics gentamicin, ciprofloxacin, vancomycin and daptomycin, but not oxacillin or clindamycin. We also found that aB promoted staphylococcal survival in whole human blood, most likely via its contribution to oxidative stress resistance. Therefore, we conclude that the general stress response of S. aureus may contribute to the development of chronic infection by conferring tolerance to both antibiotics and host immune defences.