NorB, an Efflux Pump in Staphylococcus aureus Strain MW2, Contributes to Bacterial Fitness in Abscesses
- 1 November 2008
- journal article
- research article
- Published by American Society for Microbiology in Journal of Bacteriology
- Vol. 190 (21), 7123-7129
- https://doi.org/10.1128/jb.00655-08
Abstract
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.Keywords
This publication has 32 references indexed in Scilit:
- The Transcriptional Regulators NorG and MgrA Modulate Resistance to both Quinolones and β-Lactams inStaphylococcus aureusJournal of Bacteriology, 2007
- Characterization of the Staphylococcus aureus Heat Shock, Cold Shock, Stringent, and SOS Responses and Their Effects on Log-Phase mRNA TurnoverJournal of Bacteriology, 2006
- CD4+T cells and CXC chemokines modulate the pathogenesis ofStaphylococcus aureuswound infectionsProceedings of the National Academy of Sciences of the United States of America, 2006
- Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threatThe Lancet, 2006
- NorC, a New Efflux Pump Regulated by MgrA of Staphylococcus aureusAntimicrobial Agents and Chemotherapy, 2006
- Approaches to Bacterial RNA Isolation and Purification for Microarray Analysis of Escherichia coli K1 Interaction with Human Brain Microvascular Endothelial CellsJournal of Clinical Microbiology, 2005
- A Gonococcal Efflux Pump System Enhances Bacterial Survival in a Female Mouse Model of Genital Tract InfectionInfection and Immunity, 2003
- Establishment of an experimental model of a Staphylococcus aureus abscess in mice by use of dextran and gelatin microcarriersJournal of Medical Microbiology, 1989
- Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mpl8 and pUC19 vectorsGene, 1985
- The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophageNature, 1983