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Title:	Molecular analysis of isoniazid and rifampin resistance in Mycobacterium tuberculosis isolates recovered from Barcelona.
Author:	Coll, Pere; Aragón, Lina Marcela; Alcaide Fernández de Vega, Fernando; Espasa, Mateo; Garrigó, Montserrat; González Martín, Julián; Manterola, Jose M.; Orús, Pilar; Salvadó, Margarita
Other authors:	Universitat de Barcelona
Abstract:	We studied the presence of mutations in the whole katG gene and specific regions of the oxyR-ahpC and mabA-inhA regulatory region in 61 Mycobacterium tuberculosis isoniazid-resistant isolates. An 81-bp region of the rpoB gene was also sequenced in 17 rifampin-resistant strains. Alterations in the katG gene were detected in 55% of the isolates. Mutation in codon 315 was the most prevalent (32%). Strains showed a high level of resistance, and most maintained a substantial catalase-peroxidase activity. Three strains with an isoniazid MIC of ≥32 µg/ml lacked catalase-peroxidase activity. Two of them had deletions in the catalytic domain of the KatG protein. One strain with deletion and three strains with mutations in the C-terminal domain showed low-level resistance and conserved the catalase-peroxidase activity. Mutations in the mabA-inhA regulatory region were identified in 32% of the isolates. All had low-level resistance, and the vast majority conserved catalase-peroxidase activity. Seventeen percent of the isoniazid-resistant isolates had no detectable alterations at the studied loci. Resistance to rifampin was associated with mutations in the 81-bp of the rpoB gene in all cases. IS6110 analysis indicated that recent transmission contributed substantially to the emergence of isoniazid- resistant tuberculosis in Barcelona through short transmission chains. A rapid genotypic assay, including the 315-katG codon and the -15 nucleotide of the mabA-inhA regulatory region, may cover 62% of isoniazid- resistant strains in Barcelona. In contrast, the targeting of the 81-bp region of rpoB would detect all our rifampin-resistant isolates.
Subject(s):	-Mycobacterium tuberculosis -Tuberculosi -Medicaments antituberculosos -Resistència als medicaments -Genètica molecular -Mycobacterium tuberculosis -Tuberculosis -Antitubercular agents -Drug resistance -Molecular genetics
Rights:	(c) Mary Ann Liebert, Inc., 2005
Document type:	Article Article - Published version
Published by:	Mary Ann Liebert, Inc.
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