Involvement of an efflux system in mediating high level of fluoroquinolone resistance in Mycobacterium smegmatis

Abstract

A wild type strain ofMycobacterium smegmatismc²155 was serially adapted to 64 fold of minimal inhibitory concentration of an antimycobacterial agent, ciprofloxacin. This clone (CIP^r) exhibited cross resistance to ofloxacin and ethidium bromide. The rate of drug efflux was accelerated in CIP^rcompared to the wild type strain. Verapamil, a calcium channel blocker, enhanced the drug accumulation in CIP^rby diminishing the efflux and thus reversed the resistant phenotype. Additionally, a missense mutation was detected in the quinolone resistance determining region of the DNA-gyrase A subunit of CIP^r. Taken together, these results suggest that drug efflux plays a major role in conferring such a high level of resistance in CIP^r, in addition to the mutation in the DNA-gyrase locus.