The Transcriptional Regulators NorG and MgrA Modulate Resistance to both Quinolones and β-Lactams inStaphylococcus aureus

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Abstract
MgrA is a known regulator of the expression of several multidrug transporters inStaphylococcus aureus. We identified another regulator of multiple efflux pumps, NorG, by its ability, like that of MgrA, to bind specifically to the promoter of the gene encoding the NorA efflux pump. NorG is a member of the family of the GntR-like transcriptional regulators, and it binds specifically to the putative promoters of the genes encoding multidrug efflux pumps NorA, NorB, NorC, and AbcA. Overexpression ofnorGproduces a threefold increase innorBtranscripts associated with a fourfold increase in the level of resistance to quinolones. In contrast, disruption ofnorGproduces no change in the level of transcripts ofnorA,norB, andnorCbut causes an increase of at least threefold in the transcript level ofabcA, associated with a fourfold increase in resistance to methicillin, cefotaxime, penicillin G, and nafcillin. Overexpression of clonedabcAcaused an 8- to 128-fold increase in the level of resistance to all four β-lactam antibiotics. Furthermore, MgrA and NorG have opposite effects onnorBandabcAexpression. MgrA acts as an indirect repressor fornorBand a direct activator forabcA, whereas NorG acts as a direct activator fornorBand a direct repressor forabcA.