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Antimicrobial Agents and Chemotherapy, December 2006, p. 4170-4173, Vol. 50, No. 12
0066-4804/06/$08.00+0     doi:10.1128/AAC.00944-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Stéphanie Matrat,1 Nicolas Veziris,1 Claudine Mayer,2 Vincent Jarlier,1 Chantal Truffot-Pernot,1 Juliette Camuset,3 Elisabeth Bouvet,4 Emmanuelle Cambau,5 and Alexandra Aubry1*

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,1 INSERM, U655-LRMA, Paris, France,2 Service de Pneumologie, Centre Hospitalier d'Argenteuil, Argenteuil, France,3 Service des Maladies Infectieuses, Faculté de Médecine René Diderot, site Bichat Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France,4 Laboratoire de Bactériologie-Virologie-Hygiène, CHU Henri Mondor, Université Paris 12, Assistance Publique-Hôpitaux de Paris, Créteil, France5

Received 31 July 2006/ Returned for modification 1 September 2006/ Accepted 21 September 2006

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.

* Corresponding author. Mailing address: Faculté de Médecine Pierre et Marie Curie, site Pitié-Salpêtrière, 91, boulevard de l'Hôpital, 75634 Paris cedex 13, France. Phone: 33 1 40 77 97 46. Fax: 33 1 45 82 75 77. E-mail: aubry{at}chups.jussieu.fr.

{triangledown} Published ahead of print on 2 October 2006.

Antimicrobial Agents and Chemotherapy, December 2006, p. 4170-4173, Vol. 50, No. 12
0066-4804/06/$08.00+0     doi:10.1128/AAC.00944-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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