Staphylococcus aureus Regulator Sigma B is Important to Develop Chronic Infections in Hematogenous Murine Osteomyelitis Model

Abstract

<i>Staphylococcus aureus</i> is a major pathogen causing bone infections that can become chronic and difficult to treat. Recently, we described the mechanism employed by <i>S. aureus</i> to switch to small colony variants (SCVs) and trigger intracellular bacterial persistence through the global stress regulator SigB. Here, we studied the role of SigB in the formation of chronic osteomyelitis. We used a murine hematogenous osteomyelitis model, where the mice were infected via the tail vein and subsequently developed chronic osteomyelitis. Mice were infected with <i>S. aureus</i> LS1, LS1Δ<i>sigB</i> and LS1Δ<i>sigB</i> complemented and kidney and bone tissues were analyzed six weeks after infection. <i>S. aureus</i> LS1Δ<i>sigB</i> formed a high rate of abscesses in kidneys, but the bacterial loads and the weight loss of the animals were lower in comparison with animals infected with the wild type and the complemented strain, indicating a more rapid and efficient bacterial clearing by the host immune system. Moreover, the <i>sigB</i>-mutant was not able to form SCV phenotypes either in kidney or in bone tissue. Our results demonstrate that staphylococcal SigB is important to avoid bacterial elimination by the host immune response, establish a bone infection and mediate bacterial adaptation (SCV-formation) for persistent infections.