Molecular Characterization of Isoniazid and Rifampin Resistance ofMycobacterium tuberculosisClinical Isolates from Malatya, Turkey

Abstract

Molecular characterization of drug resistance of Mycobacterium tuberculosis strains of different origins can generate information useful for developing molecular methods that are widely applicable for rapid drug resistance detection. Using DNA sequencing and allele-specific polymerase chain reaction (AS-PCR), we investigated genetic mutations associated with isoniazid (INH) and rifampin (RIF) resistance among 29 drug-resistant clinical isolates of M. tuberculosis collected from Malatya, Turkey, including 19 multi-drug-resistant (MDR) isolates. Point mutations were detected at codons 531, 516, 526, and 513 of the RNA polymerase beta- subunit gene (rpoB) in 10 (47.6%), five (23.8%), three (14.3%), and three (14.3%) of the 21 RIF-resistant isolates, respectively. Of the five isolates having mutations in codon 516, three also had mutations at codon 527; one had a concurrent mutation at codon 572. Mutations at codon 315 of the catalase-peroxidase-encoding gene (katG) were found in 17 (63.0%) of the 27 INH-resistant isolates. Interestingly, the katG codon 315 mutation was observed at a much higher frequency in MDR isolates than in INH-mono-resistant isolates ( approximately 79% vs. 25%). This study provided the first molecular characterization of INH and RIF resistance of M. tuberculosis clinical isolates from Eastern Turkey, and extended our knowledge of molecular basis of M. tuberculosis drug resistance.

Molecular Characteristics of Rifampin- and Isoniazid-Resistant Mycobacterium tuberculosis Strains Isolated in Vietnam

“…Several recent studies revealed that mutations associated with RIF resistance can also be located outside the 81-bp rpoB core region, although this does not occur frequently. Examples are ATC to TTC at codon 572 (1,32), CAG to CAT at codon 490 (5), GGG to GAG at codon 534, and CCC to CAC at codon 535 (18). Another possibility is that for this resistant strain, changes have occurred in genes whose products participate in antibiotic permeation or metabolism (14).…”

Extremely high prevalence of multidrug resistant tuberculosis in Murmansk, Russia: a population-based study

“…Based on the fingerprinting data, no indication of dual infection was found in these isolates. Dual or multiple mutations in the rpoB have been reported Kazakhstan [37], Turkey [39] Belarus [40] and South Korea [41] to mention a few.…”

Evaluation of the Genotype MTBDR Assay for Rapid Detection of Rifampin and Isoniazid Resistance in Mycobacterium tuberculosis Isolates

“…The incidence of pulmonary tuberculosis in Turkey is nearly 30 per 100,000 population (2,26). In the Aegean region, 8.2% of M. tuberculosis strains isolated between 1999 and 2001 were found to be resistant to rifampin (RIF).…”