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.
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.
Matrat
Stéphanie
S
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.
Veziris
Nicolas
N
Mayer
Claudine
C
Jarlier
Vincent
V
Truffot-Pernot
Chantal
C
Camuset
Juliette
J
Bouvet
Elisabeth
E
Cambau
Emmanuelle
E
Aubry
Alexandra
A
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
D000995:Antitubercular Agents; D024841:Fluoroquinolones; D027081:DNA Gyrase