Fluoroquinolone resistance associated with specific gyrase mutations in clinical isolates of multidrug-resistant Mycobacterium tuberculosis.
Fluoroquinolones are potent antibacterial agents being used clinically against multidrug-resistant tuberculosis. Treatment failure is thought to arise from acquisition of fluoroquinolone resistance by Mycobacterium tuberculosis. A collection of 13 resistant clinical isolates of M. tuberculosis was examined for ciprofloxacin sensitivity relative to controls exhibiting the same IS6110 DNA type. Specific alleles were associated with distinct levels of drug susceptibility for 11 isolates that contained nucleotide changes expected to alter the amino acid sequence of the A subunit of DNA gyrase. Five different gyrA (ciprofloxacin resistance) alleles were present among 7 isolates having the W DNA subtype. These isolates, which are representative of an outbreak strain, constitute a panel of organisms that can be used to evaluate contributions of gyrase and DNA topoisomerase IV to resistance.
Xu
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Public Health Research Institute, New York, New York 10016, USA.
Kreiswirth
B N
BN
Sreevatsan
S
S
Musser
J M
JM
Drlica
K
K
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000502:physiology; D018432:Drug Resistance, Multiple; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology
D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D004250:DNA Topoisomerases, Type II