Predominance of drug resistant M. tuberculosis isolates of the

Information on genomic diversity among M. tuberculosis isolates is limited due to lack of systematic analysis using multiple markers. With an aim to delineate the genetic makeup of major circulating lineages/sub-lineages in Delhi, we performed in-depth analysis of M. tuberculosis isolates using two rapid PCR-based molecular genotyping techniques, in addition to single nucleotide polymorphism (SNP) analysis and large deletion typing, The results from the genotyping analysis showed that the majority (60 of 65) of the isolates belonged to 21 previously described genotypes, assigned to 10 different lineages/families of M. tuberculosis and that 44 out of the 65 isolates were unique strains. The most frequent lineage was the CAS1_DELHI (46.2 %), which previously has been shown to be highly common in this area. On combining the results from genotyping with the results from the SNP analysis, we could discriminate between 13 of the 21 clustered isolates. Further analysis of the SNP results revealed a novel lineage-specific silent mutation (Figure) in a gene coding for resistance to one of the anti-tuberculosis drugs, pyrazinamide. SNP analysis also revealed several other mutations in genes conferring resistance to 4 of the key first-line anti-tuberculosis drugs; rifampicin, isoniazid, and ethambutol, in addition to PZA, suggesting that there is a high frequency of circulating drug-resistant M. tuberculosis isolates in New Delhi.

Link to the full article in PLoS ONE: http://xrl.us/beitx6

Results from genotyping analysis Foto: UiB