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PMID: 15388427 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

AcrAB-TolC directs efflux-mediated multidrug resistance in Salmonella enterica serovar typhimurium DT104.

Antimicrobial agents and chemotherapy ·Vol. 48 ·No. 10 ·2004-10-00 ·Pages 3729-35

Baucheron S, Tyler S, Boyd D, Mulvey MR, Chaslus-Dancla E, Cloeckaert A

Abstract

Multidrug-resistant Salmonella enterica serovar Typhimurium definitive phage type 104 (DT104) strains harbor a genomic island, called Salmonella genomic island 1 (SGI1), which contains an antibiotic resistance gene cluster conferring resistance to ampicillin, chloramphenicol, florfenicol, streptomycin, sulfonamides, and tetracyclines. They may be additionally resistant to quinolones. Among the antibiotic resistance genes there are two, i.e., floR and tet(G), which code for efflux pumps of the major facilitator superfamily with 12 transmembrane segments that confer resistance to chloramphenicol-florfenicol and the tetracyclines, respectively. In the present study we determined, by constructing acrB and tolC mutants, the role of the AcrAB-TolC multidrug efflux system in the multidrug resistance of several DT104 strains displaying additional quinolone resistance or not displaying quinolone resistance. This study shows that the quinolone resistance and the decreased fluoroquinolone susceptibilities of the strains are highly dependent on the AcrAB-TolC efflux system and that single mutations in the quinolone resistance-determining region of gyrA are of little relevance in mediating this resistance. Overproduction of the AcrAB efflux pump, as determined by Western blotting with an anti-AcrA polyclonal antibody, appeared to be the major mechanism of resistance to quinolones. Moreover, chloramphenicol-florfenicol and tetracycline resistance also appeared to be highly dependent on the presence of AcrAB-TolC, since the introduction of mutations in the respective acrB and tolC genes resulted in a susceptible or intermediate resistance phenotype, according to clinical MIC breakpoints, despite the presence of the FloR and Tet(G) efflux pumps. Resistance to other antibiotics, ampicillin, streptomycin, and sulfonamides, was not affected in the acrB and tolC mutants of DT104 strains harboring SGI1. Therefore, AcrAB-TolC appears to direct efflux-mediated resistance to quinolones, chloramphenicol-florfenicol, and tetracyclines in multidrug-resistant S. enterica serovar Typhimurium DT104 strains.

MeSH Terms
Bacterial Proteins/drug effects,genetics,metabolism Blotting, Western Carrier Proteins/drug effects,genetics,metabolism Drug Resistance, Multiple, Bacterial/genetics Genes, Bacterial/genetics Mutation/genetics Reverse Transcriptase Polymerase Chain Reaction Salmonella typhimurium/drug effects,genetics,metabolism
Chemicals
AcrAB-TolC protein, Salmonella enterica Bacterial Proteins Carrier Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Baucheron Sylvie
Unité BioAgresseurs, Santé et Environnement, Institut National de la Recherche Agronomique, 37380 Nouzilly, France.
Tyler Shaun
Boyd David
Mulvey Michael R
Chaslus-Dancla Elisabeth
Cloeckaert Axel
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Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.48.10.3729-3735.2004
Published
2004-10-00
Pages
3729-35
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC521921
Subset
IM
Corrections
CommentIn
PMID: 19570753
External Links
PubMed source DOI: 10.1128/AAC.48.10.3729-3735.2004 PMC Full Text View journal details
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