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Journal of Bacteriology, November 2008, p. 7123-7129, Vol. 190, No. 21
0021-9193/08/$08.00+0     doi:10.1128/JB.00655-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

NorB, an Efflux Pump in Staphylococcus aureus Strain MW2, Contributes to Bacterial Fitness in Abscesses{triangledown}

Yanpeng Ding,1 Yoshikuni Onodera,1,{dagger} Jean C. Lee,2 and David C. Hooper1*

Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114,1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, Massachusetts 021152

Received 9 May 2008/ Accepted 9 August 2008

While remaining a major problem in hospitals, Staphylococcus aureus is now spreading in communities. Strain MW2 (USA400 lineage) and other community methicillin-resistant S. aureus strains most commonly cause skin infections with abscess formation. Multidrug resistance (MDR) efflux pumps contribute to antimicrobial resistance but may also contribute to bacterial survival by removal of environmental toxins. In S. aureus, NorA, NorB, NorC, and Tet38 are chromosomally encoded efflux pumps whose overexpression can confer MDR to quinolones and other compounds (Nor pumps) or tetracyclines alone (Tet38), but the natural substrates of these pumps are not known. To determine the role of these efflux pumps in a natural environment in the absence of antibiotics, we used strain MW2 in a mouse subcutaneous abscess model and compared pump gene expression as determined by reverse transcription-PCR in the abscesses and in vitro. norB and tet38 were selectively upregulated in vivo more than 171- and 24-fold, respectively, whereas norA and norC were downregulated. These changes were associated with an increase in expression of mgrA, which encodes a transcriptional regulator known to affect pump gene expression. In competition experiments using equal inocula of a norB or tet38 mutant and parent strain MW2, each mutant exhibited growth defects of about two- to threefold in vivo. In complementation experiments, a single-copy insertion of norB (but not a single-copy insertion of tet38) in the attB site within geh restored the growth fitness of the norB mutant in vivo. Our findings indicate that some MDR pumps, like NorB, can facilitate bacterial survival when they are overexpressed in a staphylococcal abscess and may contribute to the relative resistance of abscesses to antimicrobial therapy, thus linking bacterial fitness and resistance in vivo.

* 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

{triangledown} Published ahead of print on 22 August 2008.

{dagger} Present address: Daiichi Pharmaceutical Co. Ltd. Tokyo R&D Center, 16-13, Kita-Kasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan.

Journal of Bacteriology, November 2008, p. 7123-7129, Vol. 190, No. 21
0021-9193/08/$08.00+0     doi:10.1128/JB.00655-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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