title: Functional analysis of DNA gyrase mutant enzymes carrying mutations at position 88 in the A subunit found in clinical strains of Mycobacterium tuberculosis resistant to fluoroquinolones.
abstract: We investigated the enzymatic efficiency and inhibition by quinolones of Mycobacterium tuberculosis DNA gyrases carrying the previously described GyrA G88C mutation and the novel GyrA G88A mutation harbored by two multidrug-resistant clinical strains and reproduced by site-directed mutagenesis. Fluoroquinolone MICs and 50% inhibitory concentrations for both mutants were 2- to 43-fold higher than for the wild type, demonstrating that these mutations confer fluoroquinolone resistance in M. tuberculosis.
authors.affiliation: Laboratoire de Bactériologie, Centre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, site Pitié-Salpêtrière, Université Paris 6, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Matrat
authors.forename: Nicolas
authors.initials: N
authors.lastname: Veziris
authors.forename: Claudine
authors.initials: C
authors.lastname: Mayer
authors.forename: Vincent
authors.initials: V
authors.lastname: Jarlier
authors.forename: Chantal
authors.initials: C
authors.lastname: Truffot-Pernot
authors.forename: Juliette
authors.initials: J
authors.lastname: Camuset
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bouvet
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Cambau
authors.forename: Alexandra
authors.initials: A
authors.lastname: Aubry
mesh_terms: D000995:Antitubercular Agents / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D027081:DNA Gyrase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D017434:Protein Structure, Tertiary
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D027081:DNA Gyrase