Involvement of an Efflux System in Mediating High Level of Fluoroquinolone Resistance inMycobacterium smegmatis

A wild type strain ofMycobacterium smegmatismc2155 was serially adapted to 64 fold of minimal inhibitory concentration of an antimycobacterial agent, ciprofloxacin. This clone (CIPr) exhibited cross resistance to ofloxacin and ethidium bromide. The rate of drug efflux was accelerated in CIPrcompared to the wild type strain. Verapamil, a calcium channel blocker, enhanced the drug accumulation in CIPrby 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 CIPr. Taken together, these results suggest that drug efflux plays a major role in conferring such a high level of resistance in CIPr, in addition to the mutation in the DNA-gyrase locus.