Rat/MgrA, a regulator of autolysis, is a regulator of virulence genes in Staphylococcus aureus.

We have previously identified mgrA (rat) as a regulator of autolysis in Staphylococcus aureus. Besides its effect on autolytic activity, we recently found alterations in the expression of regulator and target virulence genes in the mgrA mutant. Northern analysis and transcription fusion assays showed that inactivation of mgrA has led to the downregulation of RNAIII of agr and hla and upregulation of sarS and spa. Although both SarA and agr are activators of alpha-hemolysin and a repressors of protein A synthesis, we found that the transcription of sarA was not affected in the mgrA mutant and vice versa, indicating that MgrA likely regulates hla and spa in a SarA-independent manner. Previously we have shown that SarT, a SarA homolog, is a repressor of hla and an activator of spa, presumably by activating SarS, however, analysis of the double sarT mgrA mutant for hla and spa transcription indicated that the mgrA-mediated effect is not mediated via sarT. Our results further demonstrated that the mgrA gene product regulates hla and spa expression in a dual fashion, with the first being agr dependent and the second agr independent. In the agr-independent pathway, MgrA binds directly to hla and the sarS promoter to modulate alpha-hemolysin and protein A expression. Thus, our studies here have defined the nature of interaction of mgrA with other regulators such as agr, sarS, and sarT and its role in regulating hla and spa transcription within the virulence regulatory network of S. aureus.