Fitness Costs of Drug-resistance Mutations in Multidrug Resistant M. tuberculosis: A Household-based Case-control Study.

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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

Abstract
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]