The mutations of katG and inhA genes of isoniazid-resistant Mycobacterium tuberculosis isolates in Taiwan.

The isoniazid (INH) resistance of Mycobacterium tuberculosis is caused by mutations in the katG and inhA genes encoding for catalase-peroxidase and inhA, respectively. Sequences of the katG and inhA gene of 70 isolates were analyzed to identify the mutations and to compare the mutations with their related susceptibilities. Sequences of the katG and inhA genes and the resistance profiles were analyzed for the 70 M. tuberculosis isolates, collected from nine hospitals in Taiwan during the period from 1999 to 2011. Fifteen alleles were identified in the katG gene and two alleles were identified in the inhA gene. Among the 15 alleles identified in the katG gene, 14 alleles were found in isolates resistant to isoniazid, while only three alleles were found in isolates susceptible to isoniazid. The mutations of the katG gene and their frequencies of 41 INH-resistant isolates were Arg463Leu (51%), Ser315Thr (29%), Ser315Asn (9.8%), and other loci (22%). The sensitivity and specificity of the Ser315Thr mutation for the detection of INH-resistant isolates were 29% and 100%, respectively. The frequency of inhA gene mutation was low (2.44%) in the 41 INH-resistant isolates. The diverse alleles of the katG gene associated with INH resistance are present in the M. tuberculosis isolates in Taiwan. These data may be applied to develop new probes for various alleles associated with INH resistance in order to increase the sensitivity for the detection of genetically diverse M. tuberculosis isolates in different geographic areas. The diversity of mutations can also provide information for investigating the evolutional lineages of M. tuberculosis isolates.

Tseng ST ，Tai CH ，Li CR ，Lin CF ，Shi ZY ... -  《-》

Molecular characterization of isoniazid-resistant Mycobacterium tuberculosis isolates from Xi'an, China.

Zhou A ，Nawaz M ，Duan Y ，Moore JE ，Millar BC ，Xu J ，Yao Y ... -  《-》

[Characterization of the katG, inhA, ahpC, kasA, and oxyR gene mutations in isoniazid-resistant and susceptible strain of Mycobacterium tuberculosis by automated DNA sequencing].

Chen X ，Ma Y ，Jin Q ，Jiang GL ，Li CY ，Wang Q ... -  《-》

Detection of mutations associated with isoniazid resistance in multidrug-resistant Mycobacterium tuberculosis clinical isolates.

To determine the prevalence of isoniazid resistance-conferring mutations among multidrug-resistant (MDR) isolates of Mycobacterium tuberculosis from Poland. Nine genetic loci, including structural genes (katG, inhA, ahpC, kasA, ndh, nat and mshA) and regulatory regions (i.e. the mabA-inhA promoter and oxyR-ahpC intergenic region) of 50 MDR M. tuberculosis isolates collected throughout Poland were PCR-amplified in their entirety and screened for mutations by direct sequencing methodology. Forty-six (92%) MDR M. tuberculosis isolates had mutations in the katG gene, and the katG Ser315Thr substitution predominated (72%). Eight (16%) isolates (six with a mutated katG allele) had mutations in the inhA promoter region and two such isolates also had single inhA structural gene mutations. Mutations in the oxyR-ahpC locus were found in five (10%) isolates, of which all but one had at least one additional mutation in katG. Mutations in the remaining genetic loci (kasA, ndh, nat and mshA) were detected in 12 (24%), 4 (8%), 5 (10%) and 17 (34%) MDR isolates, respectively. All non-synonymous mutants for these genes harboured mutations in katG. One isolate had no mutations in any of the analysed loci. This study accentuates the usefulness of katG and inhA promoter mutations as predictive markers of isoniazid resistance. Testing only for katG 315 and inhA -15 mutations would detect isoniazid resistance in 84% of the MDR M. tuberculosis sample. This percentage would increase to 96% if the sequence analysis was extended to the entire katG gene. Analysis of the remaining genetic loci did not contribute greatly to the identification of isoniazid resistance.

Jagielski T ，Bakuła Z ，Roeske K ，Kamiński M ，Napiórkowska A ，Augustynowicz-Kopeć E ，Zwolska Z ，Bielecki J ... -  《-》

The impact of combined gene mutations in inhA and ahpC genes on high levels of isoniazid resistance amongst katG non-315 in multidrug-resistant tuberculosis isolates from China.

Liu L ，Jiang F ，Chen L ，Zhao B ，Dong J ，Sun L ，Zhu Y ，Liu B ，Zhou Y ，Yang J ，Zhao Y ，Jin Q ，Zhang X ... -  《Emerging Microbes & Infections》