Journal of Bacteriology, May 2003, p. 3127-3138, Vol. 185, No. 10
0021-9193/03/$08.00+0 DOI: 10.1128/JB.185.10.3127-3138.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Characterization of NorR Protein, a Multifunctional Regulator of norA Expression in Staphylococcus aureus
Que Chi Truong-Bolduc,1 Xiamei Zhang,1 and David C. Hooper1,2*
Division of Infectious Diseases and Medical Services, Massachusetts General Hospital,1
Harvard Medical School, Boston, Massachusetts 02114-26962
Received 17 December 2002/
Accepted 28 February 2003
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
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.
* Corresponding author. Mailing address: Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114-2696. Phone: (617) 726-3812. Fax: (617) 726-7416. E-mail: dhooper{at}partners.org.
Journal of Bacteriology, May 2003, p. 3127-3138, Vol. 185, No. 10
0021-9193/03/$08.00+0 DOI: 10.1128/JB.185.10.3127-3138.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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Copyright © 2003 by the American Society for Microbiology. All rights reserved.