title: Investigation of Ser315 substitutions within katG gene in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from south India.
abstract: Mutation at codon 315 of katG gene is the major cause for isoniazid (INH) resistance in Mycobacterium tuberculosis (M. tuberculosis). Substitution at codon 315 of katG gene was analyzed in 85 phenotypically resistant isolates collected from various parts of southern India by direct sequencing method. The obtained results were interpreted in the context of minimum inhibitory concentration (MIC) of INH. Of the 85 phenotypically resistant isolates, 56 (66%) were also correlated by the presence of resistance mutations in the katG gene; 47 of these isolates had ACC, 6 had AAC, 2 had ATC, and one had CGC codon. The frequency of Ser315 substitution in katG gene was found to be higher (70%) amongst multidrug-resistant (MDR) strains than among non-MDR (61%) INH-resistant isolates. Further, the frequency of mutations was found to be greater (74%) in isolates with higher MIC values in contrast to those isolates with low MIC values (58%). Therefore, the study identified high prevalence of Ser315Thr substitution in katG gene of INH-resistant isolates from south India. Also, isolates harboring this substitution were found to be associated with multidrug and high level INH resistance.
authors.affiliation: Division of Biomedical Informatics, Department of Clinical Research, National Institute for Research in Tuberculosis (NIRT), Indian Council of Medical Research (ICMR), No. 1 Mayor Sathyamoorthy Road, Chetput, Chennai, Tamil Nadu 600 031, India.
authors.forename: A Nusrath
authors.initials: AN
authors.lastname: Unissa
authors.affiliation: Division of Biomedical Informatics, Department of Clinical Research, National Institute for Research in Tuberculosis (NIRT), Indian Council of Medical Research (ICMR), No. 1 Mayor Sathyamoorthy Road, Chetput, Chennai, Tamil Nadu 600 031, India.
authors.forename: N
authors.initials: N
authors.lastname: Selvakumar
authors.affiliation: Division of Biomedical Informatics, Department of Clinical Research, National Institute for Research in Tuberculosis (NIRT), Indian Council of Medical Research (ICMR), No. 1 Mayor Sathyamoorthy Road, Chetput, Chennai, Tamil Nadu 600 031, India.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Division of Biomedical Informatics, Department of Clinical Research, National Institute for Research in Tuberculosis (NIRT), Indian Council of Medical Research (ICMR), No. 1 Mayor Sathyamoorthy Road, Chetput, Chennai, Tamil Nadu 600 031, India.
authors.forename: C
authors.initials: C
authors.lastname: Suganthi
authors.affiliation: Division of Biomedical Informatics, Department of Clinical Research, National Institute for Research in Tuberculosis (NIRT), Indian Council of Medical Research (ICMR), No. 1 Mayor Sathyamoorthy Road, Chetput, Chennai, Tamil Nadu 600 031, India.
authors.forename: L E
authors.initials: LE
authors.lastname: Hanna
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D002374:Catalase / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D006801:Humans; D007194:India; D007538:Isoniazid; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000235:genetics*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D003062:Codon; D004269:DNA, Bacterial; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D007538:Isoniazid