Evidence for an efflux pump mediating multiple antibiotic resistance in Salmonella enterica serovar Typhimurium

The mechanism of multiple antibiotic resistance in six isolates of Salmonel la enterica serovar Typhimurium recovered from a patient treated with cipro floxacin was studied to investigate the role of efflux in the resistance ph enotype. Compared to the patient's pretherapy isolate (L3), five of six iso lates accumulated less ciprofloxacin, three of six isolates accumulated les s chloramphenicol, and all six accumulated less tetracycline. The accumulat ion of one or more antibiotics was increased by carbonyl cyanide m-chloroph enylhydrazone to concentrations similar to those accumulated by L3 for all isolates except one, in which accumulation of all three agents remained app roximately half that of L3, All isolates had the published wild-type sequen ces of marO and marR, No increased expression of marA, tolC, or soxS was ob served by Northern blotting; however, three isolates showed increased expre ssion of acrB, which was confirmed by quantitative competitive reverse tran scription-PCR. However, there were no mutations within acrR or the promoter region of acrAB in any of the isolates.