title: Sensitivities of ciprofloxacin-resistant Mycobacterium tuberculosis clinical isolates to fluoroquinolones: role of mutant DNA gyrase subunits in drug resistance.
abstract: Minimum inhibitory concentrations of sitafloxacin, gatifloxacin, moxifloxacin, sparfloxacin, levofloxacin and ciprofloxacin against 59 ciprofloxacin-resistant clinical isolates of Mycobacterium tuberculosis from Japan were determined. The isolates were most susceptible to sitafloxacin and gatifloxacin. To understand better the basis for drug resistance, nucleotide sequences encoding the gyrA and gyrB quinolone resistance-determining region were determined. Predicted amino acid sequences revealed distinct mutational patterns likely to be responsible for fluoroquinolone resistance. Double gyrA mutations as well as mutations in both gyrA and gyrB correlated with increased resistance to all fluoroquinolones.
authors.affiliation: Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Kita 20-Nishi 10, Kita-ku, Sapporo 001-0020, Japan. suzuki@czc.hokudai.ac.jp
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Chie
authors.initials: C
authors.lastname: Nakajima
authors.forename: Aki
authors.initials: A
authors.lastname: Tamaru
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuba
authors.forename: Hajime
authors.initials: H
authors.lastname: Saito
mesh_terms: D019943:Amino Acid Substitution; D000995:Antitubercular Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D007564:Japan; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D021122:Protein Subunits / Q000235:genetics; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D021122:Protein Subunits; D002939:Ciprofloxacin; D027081:DNA Gyrase