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

Susham Ingavale, Willem Van Wamel, Thanh T. Luong, Chia Y. Lee, Ambrose L. Cheung*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

126 Citations (Scopus)


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 α-hemolysin and a repressers 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 represser 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 mgn4-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 α-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.

Original languageEnglish
Pages (from-to)1423-1431
Number of pages9
JournalInfection and Immunity
Issue number3
Publication statusPublished - 1 Mar 2005
Externally publishedYes


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