Multidrug resistance in Staphylococcus aureus due to overexpression of a novel multidrug and toxin extrusion (MATE) transport protein.
Efflux is an important mechanism of multidrug resistance (MDR) in bacteria. The multidrug and toxin extrusion (MATE) family is the most recently described group of MDR efflux proteins, none of which have previously been identified in Staphylococcus aureus. Two independently derived S. aureus mutants having efflux-related MDR phenotypes were studied using microarray technology and a marked overexpression of an open reading frame (ORF; mepA) encoding a protein homologous with MATE family proteins was observed in both. There was concomitant overexpression of ORFs in close proximity to mepA (approximately 100 bp) encoding a MarR-type regulator (mepR, upstream of mepA) and a protein of unknown function (mepB, downstream). Experiments in which mepA was overexpressed or disrupted revealed that the encoded protein has a broad substrate profile that includes several monovalent and divalent biocides and the fluoroquinolone antimicrobial agents norfloxacin and ciprofloxacin. The function of MepB is obscure, it does not contribute to the MDR phenotype conferred by MepA. MepR overexpression reversed the MDR phenotypes of both mutants by repressing mepA transcription. All three ORFs are preferentially transcribed as a single mepRAB unit, suggesting that the three genes form an operon.
Kaatz
Glenn W
GW
The John D. Dingell Department of Veteran's Affairs Medical Center, Detroit, MI 48201, USA. gkaatz@juno.com
McAleese
Fionnuala
F
Seo
Susan M
SM
D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D016360:Clostridioides difficile / Q000187:drug effects / Q000235:genetics; D019295:Computational Biology; D003470:Culture Media; D017931:DNA Primers; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D019450:Genes, MDR / Q000235:genetics*; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D012097:Repressor Proteins / Q000235:genetics; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D003470:Culture Media; D017931:DNA Primers; D007202:Indicators and Reagents; D012097:Repressor Proteins