Fitness Costs of Drug-resistance Mutations in Multidrug Resistant M. tuberculosis: A Household-based Case-control Study.
J Infect Dis. 2015 Jun 19;
Authors: Salvatore PP, Becerra MC, Zur Wiesch PA, Hinkley T, Kaur D, Sloutsky A, Cohen T
BACKGROUND: The projected long-term prevalence of multidrug resistant tuberculosis (MDR-TB) depends upon the relative fitness of MDR-TB strains compared with non-MDR strains. While many experimental models have tested the in vitro or in vivo fitness costs of various drug-resistance mutations, fewer epidemiologic studies have attempted to validate these experimental findings.
METHODS: We performed a case-control study comparing drug-resistance associated mutations from MDR-TB strains causing multiple cases in a household to matched MDR strains without evidence of secondary household cases.
RESULTS: 88 multiple-case and 88 single-case household MDR strains were analyzed for 10 specific drug resistance-associated polymorphisms previously associated with fitness effects. We found that the isoniazid-resistant katG Ser315Thr mutation occurred more than twice as frequently in multiple-case households as in single-case households (OR: 2.39; 95% CI, 1.21-4.70), corroborating previous experimental findings. However, strains carrying both the katG Ser315Thr mutation and the rpsL Lys43Arg mutation were less likely to be found in multiple-case households (OR: 0.09; 95% CI, .01-.73), suggesting a negative epistatic interaction which contrasts previous findings.
CONCLUSIONS: The case-control design presents a useful approach for assessing in vivo fitness effects of drug-resistance mutations.
PMID: 26092854 [PubMed - as supplied by publisher]