ABSTRACT: The success of Staphylococcus aureus as a pathogen results from the production of a wealth of virulence determinants that aid in immune evasion, host cell invasion and dissemination of infection. Given the niche specific roles of these factors in infection, their production is controlled by a complex network of regulatory factors. In a continued effort to understand this network, the present study is aimed at characterizing the role of the transcriptional regulator XdrA and its effects on S. aureus gene expression. Using an unbiased global analysis, we find that XdrA has a broad impact on gene expression, influencing the transcription of several important virulence determinants, and factors involved in gene regulation. When assessing the role of XdrA in virulence, we find that an xdrA mutant has an increased ability to survive in whole human blood, mediated in part by increased survival within neutrophils, and an upregulation in expression of several factors involved in immune evasion, including sbi, fnbpA and efb. Furthermore, the increased survival within neutrophils appears to result from an upregulation in expression of sodM, recA, and sae, all of which assist bacterial cells in combating the effects of oxidative stress. In addition to these changes, we find that the xdrA mutant has a decreased abundance of cytolytic toxins, likely resulting from changes in agr and sae activity. We suggest that the broad impact of XdrA on the expression of genes involved in immune evasion, DNA damage, and oxidative stress tolerance, collectively result in a survival advantage allowing for the increased ability to causes disease in vivo, when xdrA is disrupted. In sum, our findings shed new light on the role of XdrA and its seemingly novel influence on S. aureus survival during infection.
