Characterization of NorR protein, a multifunctional regulator of norA expression in Staphylococcus aureus.
We characterized a Staphylococcus aureus norA gene expression regulator, NorR, initially identified from its binding to the norA promoter. The norR gene was 444 bp in length, located approximately 7 kb upstream from the norA gene, and encoded a predicted 17.6-kDa protein. Overexpression of norR in wild-type S. aureus strain ISP794 led to a fourfold decrease in sensitivity to quinolones and ethidium bromide and an increase in the level of norA transcripts, suggesting that NorR acts as a positive regulator of norA expression. Overexpression of norR in sarA and agr mutants did not alter quinolone sensitivity or levels of norA transcription, indicating that the presence of these two global regulatory systems is necessary for NorR to affect the expression of norA. Insertion and disruption of norR in ISP794 increased resistance to quinolones by 4- to 16-fold but had no effect on norA transcription, suggesting that NorR acts as a repressor for another unidentified efflux pump or pumps. These mutants also exhibited an exaggerated clumping phenotype in liquid media, which was complemented fully by a plasmid-encoded norR gene. Collectively, these results indicate that NorR is a multifunctional regulator, affecting cell surface properties as well as the expression of NorA and likely other multidrug resistance efflux pumps.
Division of Infectious Diseases and Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114-2696, USA.
Que Chi
QC
Truong-Bolduc
Xiamei
X
Zhang
David C
DC
Hooper
D001426:Bacterial Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005809:Genes, Regulator; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009154:Mutation; D011401:Promoter Regions, Genetic; D015363:Quinolones / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015363:Quinolones; D012333:RNA, Messenger; D014157:Transcription Factors; C474646:NorR protein, Staphylococcus aureus; C075040:NorA protein, Staphylococcus