Involvement of an efflux system in mediating high level of fluoroquinolone resistance in Mycobacterium smegmatis.
A wild type strain of Mycobacterium smegmatis mc2 155 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 CIPr compared to the wild type strain. Verapamil, a calcium channel blocker, enhanced the drug accumulation in CIPr by 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.
Banerjee
S K
SK
Division of Molecular Biology, Institute of Microbial Technology, Chandigarh, India.
Bhatt
K
K
Rana
S
S
Misra
P
P
Chakraborti
P K
PK
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001483:Base Sequence; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004269:DNA, Bacterial; D004352:Drug Resistance, Microbial / Q000235:genetics; D024841:Fluoroquinolones; D008969:Molecular Sequence Data; D009154:Mutation; D009161:Mycobacterium / Q000187:drug effects* / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D014700:Verapamil; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II