Journal
NATURE GENETICS
Volume 44, Issue 1, Pages 106-U147Publisher
NATURE PORTFOLIO
DOI: 10.1038/ng.1038
Keywords
-
Categories
Funding
- US National Institute of Allergy and Infectious Disease, US National Institutes of Health
- US Department of Health and Human Services [HHSN266200400001C, AI090928, AI034238]
- Medical Research Council, UK [MRC_U117588500]
- Swiss National Science Foundation [PP00A-119205]
- European Community [QLK-CT-2002-01612, FP7-223681]
- MRC [MC_U117581288] Funding Source: UKRI
- Medical Research Council [MC_U117581288] Funding Source: researchfish
Ask authors/readers for more resources
Epidemics of drug-resistant bacteria emerge worldwide, even as resistant strains frequently have reduced fitness compared to their drug-susceptible counterparts(1). Data from model systems suggest that the fitness cost of antimicrobial resistance can be reduced by compensatory mutations(2); however, there is limited evidence that compensatory evolution has any significant role in the success of drug-resistant bacteria in human populations(3-6). Here we describe a set of compensatory mutations in the RNA polymerase genes of rifampicin-resistant M. tuberculosis, the etiologic agent of human tuberculosis (TB). M. tuberculosis strains harboring these compensatory mutations showed a high competitive fitness in vitro. Moreover, these mutations were associated with high fitness in vivo, as determined by examining their relative clinical frequency across patient populations. Of note, in countries with the world's highest incidence of multidrug-resistant (MDR) TB7, more than 30% of MDR clinical isolates had this form of mutation. Our findings support a role for compensatory evolution in the global epidemics of MDR TB8.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available