pncA and rpoB mutations in Mycobacteriumtuberculosis, a 3-year experiment in Lyon, France

Abstract number: 1733_1495

Mignard S., Carret G., Chomarat M., Fredenucci I., de Montclos M., Flandrois J.

The emergence of drug resistant Mycobacteriumtuberculosis is a serious public health problem. Pyrazinamide and rifampicin are first line drugs and their efficacy can be evaluated by DNA sequencing. We realised rpoB and pncA sequencing for all MTBC isolated from 2003 to 2006 in order to check the different mutations existing in Lyon, France. The in vitro susceptibility testing was done in the same time. 330 isolates of MTBC were studied during this 3-year period. On the rpoB gene, 9 mutations have been reported, 6 have ever been described: H526L (n = 1), S531L (n = 3), L511P (n = 1) and the deletion of nucleotides 514–516. 3 mutations were unknown N518D (n = 1), S469L (n = 2) but for these strains isolates were susceptible to rifampicin by in vitro testing. On the pncA gene 22 mutations have been reported. Among the 17 ever known in the literature, 10 correspond to the well known H57D mutation of M. bovis strains and 7 were T87M mutations. This last mutation is described in the literature associated with a deletion conferring resistance to pyrazinamide. All our T87M mutated strains were susceptible to pyrazinamide in vitro (none presented the deletion). Five mutations were unknown: A146V (n = 1), R2W (n = 1), H43Y (n = 1), L19P (n = 1) and V21A (n = 1). Only the A146V strain appeared resistant to pyrazinamide. The conclusion of this study is the emergence of the T87M mutation on pncA gene among strains that remain susceptible to pyrazinamide in vitro. No relationships were observed between patients by spoligotypes and MIRU types' comparison.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
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