Staphylococcus aureus dynamically adapts global regulators and virulence factor expression in the course from acute...

Staphylococcus aureus is an important pathogen of severe invasive tissue infection, e.g. osteomyelitis that can develop to chronicity and become extremely difficult to treat. Recent research revealed that S. aureus can dynamically switch to small colony variants (SCVs) that are adapted bacterial phenotypes for long-term persistence. The underlying mechanisms of the bacterial switching and adaptation process are largely dependent on an intact Sigma B regulon. As SigB is known as a transcription factor that modulates the stress response of several Gram-positive bacteria, it is most likely required by the bacteria to cope with the intracellular stress conditions. Here, we demonstrate in a long-term infection model of human osteoblasts that S. aureus continuously upregulated the expression of SigB during intracellular persistence. The increased SigB expression was accompanied by upregulation of adhesins and downregulation of toxins, which are characteristics for SCV phenotypes. These data further stress the role of SigB during chronic infections that could be a novel target for preventive or therapeutic measures to avoid chronic infections.