Evidence for an efflux pump mediating multiple antibiotic resistance in Salmonella enterica serovar Typhimurium.
The mechanism of multiple antibiotic resistance in six isolates of Salmonella enterica serovar Typhimurium recovered from a patient treated with ciprofloxacin was studied to investigate the role of efflux in the resistance phenotype. Compared to the patient's pretherapy isolate (L3), five of six isolates accumulated less ciprofloxacin, three of six isolates accumulated less chloramphenicol, and all six accumulated less tetracycline. The accumulation of one or more antibiotics was increased by carbonyl cyanide m-chlorophenylhydrazone to concentrations similar to those accumulated by L3 for all isolates except one, in which accumulation of all three agents remained approximately half that of L3. All isolates had the published wild-type sequences of marO and marR. No increased expression of marA, tolC, or soxS was observed by Northern blotting; however, three isolates showed increased expression of acrB, which was confirmed by quantitative competitive reverse transcription-PCR. However, there were no mutations within acrR or the promoter region of acrAB in any of the isolates.
Piddock
L J
LJ
Antimicrobial Agents Research Group, Division of Infection and Immunity, University of Birmingham, Birmingham, B15 2TT, United Kingdom. l.j.v.piddock@bham.ac.uk
White
D G
DG
Gensberg
K
K
Pumbwe
L
L
Griggs
D J
DJ
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple / Q000502:physiology*; D029968:Escherichia coli Proteins; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D019779:Salmonella enterica / Q000187:drug effects* / Q000378:metabolism
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012097:Repressor Proteins; C083496:AcrB protein, E coli; C080002:MarA protein, E coli; C080004:MarR protein, E coli