Repression of Capsule Production by XdrA and CodY in Staphylococcus aureus

Capsule is one of many virulence factors produced by , and its expression is highly regulated. Here, we report the repression of capsule by direct interaction of XdrA and CodY with the capsule promoter region. We found, by footprinting analyses, that XdrA repressed capsule by binding to a broad region that extended from upstream of the -35 region of the promoter to the coding region of , the first gene of the 16-gene operon. Footprinting analyses also revealed that CodY bound to a large region that overlapped extensively with that of XdrA. We found that repression of the genes in the mutant could be achieved by the overexpression of but not vice versa, suggesting is epistatic to However, we found XdrA had no effect on CodY expression. These results suggest that XdrA plays a secondary role in capsule regulation by promoting CodY repression of the genes. Oxacillin slightly induced expression and reduced promoter activity, but the effect of oxacillin on capsule was not mediated through XdrA. employs a complex regulatory network to coordinate the expression of various virulence genes to achieve successful infections. How virulence genes are coordinately regulated is still poorly understood. We have been studying capsule regulation as a model system to explore regulatory networking in In this study, we found that XdrA and CodY have broad binding sites that overlap extensively in the capsule promoter region. Our results also suggest that XdrA assists CodY in the repression of capsule. As capsule gene regulation by DNA-binding regulators has not been fully investigated, the results presented here fill an important knowledge gap, thereby further advancing our understanding of the global virulence regulatory network in .