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

Author:

Matrat Stéphanie1,Veziris Nicolas1,Mayer Claudine2,Jarlier Vincent1,Truffot-Pernot Chantal1,Camuset Juliette3,Bouvet Elisabeth4,Cambau Emmanuelle5,Aubry Alexandra1

Affiliation:

1. 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

2. INSERM, U655-LRMA, Paris, France

3. Service de Pneumologie, Centre Hospitalier d'Argenteuil, Argenteuil, France

4. Service des Maladies Infectieuses, Faculté de Médecine René Diderot, site Bichat Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France

5. Laboratoire de Bactériologie-Virologie-Hygiène, CHU Henri Mondor, Université Paris 12, Assistance Publique-Hôpitaux de Paris, Créteil, France

Abstract

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 .

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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