科研之友
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摘要
The aim of the present study was to investigate the mutational characteristics of drug-resistant genetic mutations in the katG gene to isoniazid (INH) in multi-drug resistant Mycobacterium tuberculosis (MDR-TB) L-form among patients with pneumoconiosis complicated with tuberculosis (TB), in order to reduce the occurrence of drug resistance in patients, and gain further insight into the mechanisms underlying drug resistance in MDR-TB L-form. A total of 114 clinically isolated strains of Mycobacterium tuberculosis (MTB)-forms were collected. The MDR-TB L-forms were identified using a conventional antimicrobial susceptibility test (AST). The DNA genomes were extracted, the target genes were amplified by polymerase chain reaction technology and the hotspot mutational regions in the katG gene were analyzed by direct sequencing. The results of AST analysis demonstrated that there were 31 strains of MDR-TB L-forms in 114 clinical isolates. The mutation rate of katG was 61.29% (19/31) in INH-resistant isolates, mainly concentrated in codon 315 (Ser315Thr, 48.39% and Ser315Asn, 9.68%) and 431 (Ala431Val, 3.23%). Base substitutions were identified, however, no multisite mutations were found. No mutations in katG were identified in 10 INH-sensitive strains that were randomly selected. INH-resistance was more severe in MDR-TB L-form isolates among patients with pneumoconiosis complicated with TB. The substitution of highly conserved amino acids encoded by the katG gene resulted in the molecular mechanisms responsible for INH resistance in MDR-TB L-form isolates. It was also verified that the katG gene was in diversiform. The katG Ser315Thr mutation is one of the main causes of resistance to INH in MDR-TB L-form isolates.
