Fitness Effect of the Isoniazid Resistance Mutation S315T of the Catalase-Peroxidase Enzyme KatG of Mycobacterium tuberculosis.

ABSTRACT: The mutation S315T of the catalase-peroxidase (CP) protein KatG of Mycobacterium tuberculosis is the most common mutation that confers resistance to the prodrug isoniazid. Here, we reconstruct its evolutionary history in 145 whole-genome sequences of M. tuberculosis from Russian hospitals, inferring 11 independent appearances of this mutation and 5 reversion events, with an estimated reversion rate 1,500 times higher than the rate of preserved nonsynonymous or intragenic mutations. This suggests that, contrary to the commonly held view, the mutation KatG(S315T) results in a fitness cost, possibly because of reduced tolerance to oxidative stress. Consistent with this interpretation, the mutant enzyme presents reduced CP activities. Applying the torsional network model (TNM), we found that t

SUBMITTER: Bastolla U 

PROVIDER: S-EPMC12242383 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature