RRC ID 35550
Author Holdsworth SR, Law CJ.
Title The major facilitator superfamily transporter MdtM contributes to the intrinsic resistance of Escherichia coli to quaternary ammonium compounds.
Journal J. Antimicrob. Chemother.
Abstract OBJECTIVES:Quaternary ammonium compounds (QACs) are used extensively as biocides and their misuse may be contributing to the development of bacterial resistance. Although the major intrinsic resistance to QACs of Gram-negative bacteria is mediated by the action of tripartite multidrug transporters of the resistance-nodulation-division family, we aimed to test if the promiscuity of the recently characterized major facilitator superfamily multidrug transporter, MdtM, from Escherichia coli enabled it also to function in the efflux of QACs.
METHODS:The ability of the major facilitator mdtM gene product, when overexpressed from multicopy plasmid, to protect E. coli cells from the toxic effects of a panel of seven QACs was determined using growth inhibition assays in liquid medium. Interaction between QACs and MdtM was studied by a combination of substrate binding assays using purified protein in detergent solution and transport assays using inverted vesicles.
RESULTS:E. coli cells that overproduced MdtM were less susceptible to the cytotoxic effects of each of the QACs tested compared with cells that did not overproduce the transporter. Purified MdtM bound each QAC with micromolar affinity and the protein utilized the electrochemical proton gradient to transport QACs across the cytoplasmic membrane. Furthermore, the results suggested a functional interaction between MdtM and the tripartite resistance-nodulation-division family AcrAB-TolC efflux system.
CONCLUSIONS:The results support a hitherto unidentified capacity for a single-component multidrug transporter of the major facilitator superfamily, MdtM, to function in the efflux of a broad range of QACs and thus contribute to the intrinsic resistance of E. coli to these compounds.
Volume 68(4)
Pages 831-9
Published 2013-4
DOI 10.1093/jac/dks491
PII dks491
PMID 23221628
MeSH Antiporters / genetics Antiporters / metabolism* Biological Transport Disinfectants / metabolism Disinfectants / pharmacology* Drug Resistance, Bacterial* Escherichia coli / drug effects* Escherichia coli / metabolism Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism* Protein Binding Quaternary Ammonium Compounds / metabolism Quaternary Ammonium Compounds / pharmacology*
IF 5.113
Times Cited 9
WOS Category PHARMACOLOGY & PHARMACY INFECTIOUS DISEASES MICROBIOLOGY
Resource
Prokaryotes E. coli ?