Mycobacterium tuberculosis Lineages Associated with Mutations and Drug Resistance in Isolates from India
Siva Kumar Shanmugam, Narender Kumar, Sembulingam Tamilzhalagan, Suresh Babu Ramalingam, Ashok Selvaraj, Udhayakumar Rajendhiran, Sudha Solaiyappan, Srikanth Tripathy, Mohan Natrajan, Chandrasekaran Padmapriyadarsini, Soumya Swaminathan, Julian Parkhill, Sharon J. Peacock, Uma Devi Ranganathan
Abstract
Current knowledge on resistance-conferring determinants in Mycobacterium tuberculosis is biased toward globally dominant lineages 2 and 4. In contrast, lineages 1 and 3 are predominant in India. We performed whole-genome sequencing of 498 MDR M. tuberculosis isolates from India to determine the prevalence of drug resistance mutations and to understand genomic diversity. Four lineages were identified although lineage 1 predominated (43%). The sensitivity of prediction for isoniazid and rifampicin was 92% and 98%, respectively. We observed lineage-specific variations in the proportion of isolates with resistance-conferring mutations, with drug resistance more common in lineages 2 and 3. Disputed mutations (codons 430, 435, 445, and 452) in the rpoB gene were more common in isolates other than lineage 2. Phylogenetic analysis and pairwise SNP difference revealed high genetic relatedness of lineage 2 isolates. WGS based resistance prediction has huge potential, but knowledge of regional and national diversity is essential to achieve high accuracy for resistance prediction.