Research Article Investigation of Ser315 Substitutions within katG Gene in Isoniazid-Resistant Clinical Isolates of Mycobacterium tuberculosis from South India A. Nusrath Unissa, N. Selvakumar, Sujatha Narayanan, C. Suganthi, and L. E. Hanna 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 Correspondence should be addressed to L. E. Hanna; hanna@trcchennai.in Received 2 July 2014; Accepted 20 October 2014 Academic Editor: Filippo Canducci Copyright © 2015 A. Nusrath Unissa et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. Te 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. Te 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%). Terefore, the study identifed high prevalence of Ser315Tr 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. 1. Introduction Although tuberculosis (TB) is a preventable, treatable, and curable disease, it still remains as a major public health problem. Te period of 6–9 months needed to treat the disease is too long, and the treatment is ofen associated with signifcant toxicity. Tese factors make patient compliance to therapy very difcult, leading to the emergence and selection of drug-resistant TB bacteria [1]. Te emergence of multidrug-resistant (MDR) TB, defned as strains which are resistant to two most potent anti-TB drugs, namely, isoniazid (INH) and rifampicin (RIF), and XDR-TB, defned as MDR-TB strains that are resistant to second-line TB drugs, that is, fuoroquinolones and at least one of the injectable aminoglycosides (capreomycin, kanamycin) or amikacin, has worsened the situation further [2]. Globally, 450,000 people developed MDR-TB in 2012; more than half of these cases were from India, China, and the Russian Federation. It is estimated that about 9.6% of MDR-TB cases had XDR- TB. About 170,000 MDR-TB deaths are estimated to have occurred in 2012 [3]. Resistance against all known anti-TB drugs has been reported. However, isolates of M. tuberculosis resistant to INH are seen with increasing frequency (1 in 10 6 ) as compared to isolates resistant to other drugs [4]. Also, resistance to INH, alone or in combination with other drugs, is now the second most common cause for resistance. Globally, it has been estimated that INH resistance was found in 10.3% of new cases and 27.7% of treated cases [5]. An earlier study based on susceptibility testing from south India also reported high resistance to INH in 15.4% of cases compared to 4.4% cases of RIF resistance [6]. INH has been used extensively as the frontline anti-TB drug and a drug of choice for chemoprophylaxis, acting as a principle component in the current six-month short course chemotherapy regimen. It has long been recognized that INH Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 257983, 5 pages http://dx.doi.org/10.1155/2015/257983