title: Molecular mechanism of rifampicin and isoniazid resistance in Mycobacterium tuberculosis from Bangladesh.
abstract: Despite having 100% coverage of directly observed treatment short-course, multi drug-resistant (MDR) tuberculosis (TB) is still increasing in Bangladesh. Early detection of MDR-TB by rapid molecular test and early initiation of treatment will effectively stop this trend. To develop rapid diagnostic tools, molecular characterization of genes conferring Mycobacterium tuberculosis resistance to rifampicin (RIF) and isoniazid (INH) will be required. Hence, this study elucidated the molecular mechanism RIF and INH resistance in 218 MDR strains from hospitalized (n = 161) and non-hospitalized (n = 57) TB patients in Bangladesh. Mutations in rpoB gene were detected in 207 (95.0%) with majority at codon 531 (52.3%). Mutations in katG or inhA or both were detected in 206 (94.5%) with majority at codon 315 of katG (83.9%). It was noteworthy that a novel C to T mutation at position -34 and G to A mutations at position -47 in inhA regulatory region were found, respectively, in combination with mutation at codon 315 of katG. This is the first comprehensive molecular analysis of rpoB and katG genes and inhA regulatory regions of MDR isolates from Bangladesh. This study provides basic data for the construction of low cost tailor-made molecular system for rapid diagnosis of MDR-TB in Bangladesh.
authors.affiliation: International Centre for Diarrheal Disease Research, Bangladesh, Bangladesh. zeaur@icddr.org
authors.forename: Zeaur
authors.initials: Z
authors.lastname: Rahim
authors.forename: Chie
authors.initials: C
authors.lastname: Nakajima
authors.forename: Rubhana
authors.initials: R
authors.lastname: Raqib
authors.forename: Khalequ
authors.initials: K
authors.lastname: Zaman
authors.forename: Hubert P
authors.initials: HP
authors.lastname: Endtz
authors.forename: Adri G M
authors.initials: AG
authors.lastname: van der Zanden
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics*; D001459:Bangladesh; D002374:Catalase / Q000187:drug effects / Q000235:genetics*; D003062:Codon; D012321:DNA-Directed RNA Polymerases; D024881:Drug Resistance, Bacterial; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D010088:Oxidoreductases / Q000187:drug effects / Q000235:genetics*; D010802:Phylogeny; D012293:Rifampin / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D003062:Codon; C505805:rpoB protein, Mycobacterium tuberculosis; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D012321:DNA-Directed RNA Polymerases; D007538:Isoniazid; D012293:Rifampin