Large-scale genomic analysis of Mycobacterium tuberculosis reveals extent of target and compensatory mutations linked to multi-drug resistant tuberculosis.

ABSTRACT: Resistance to isoniazid (INH) and rifampicin (RIF) first-line drugs in Mycobacterium tuberculosis (Mtb), together called multi-drug resistance, threatens tuberculosis control. Resistance mutations in katG (for INH) and rpoB (RIF) genes often come with fitness costs. To overcome these costs, Mtb compensatory mutations have arisen in rpoC/rpoA (RIF) and ahpC (INH) loci. By leveraging the presence of known compensatory mutations, we aimed to detect novel resistance mutations occurring in INH and RIF target genes. Across ~ 32 k Mtb isolates with whole genome sequencing (WGS) data, there were 6262 (35.7%) with INH and 5435 (30.7%) with RIF phenotypic resistance. Known mutations in katG and rpoB explained ~ 99% of resistance. However, 188 (0.6%) isolates had ahpC compensatory mutations with no k

SUBMITTER: Napier G 

PROVIDER: S-EPMC9837068 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature