ArticleEvolution, medicine, and public health2013
Epistasis between antibiotic resistance mutations drives the evolution of extensively drug-resistant tuberculosis.
Article in Evolution, medicine, and public health, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed.
- Polymorphisms in a bacterial signalling pathway alter evolutionary routes of antibiotic resistance in Escherichia coli.PLoS biology · 2026Article
- HyperdCas12a-based multiplexed genetic regulation in Candida albicans.Nucleic acids research · 2025Article
- Unraveling Epistatic Interactions Between Sites Under Drug-Dependent Selection in the Mycobacterium tuberculosis Genome.Molecular biology and evolution · 2025Article
- Fitness costs of Mycobacterium tuberculosis resistant to rifampicin is compensated by rapid Th2 polarization mediated by early and high IL-4 production during mice infection.Scientific reports · 2025Article
- Rifampicin and isoniazid resistance not promote fluoroquinolone resistance in Mycobacterium smegmatis.PloS one · 2025Article
- Genotypic analysis of drug-resistant tuberculosis in Ghana: Insights into pre-XDR and XDR-TB.PloS one · 2025Article
- Universal Lineage-Independent Markers of Multidrug Resistance inMicroorganisms · 2024Article
- Opinion review of drug resistant tuberculosis in West Africa: tackling the challenges for effective control.Frontiers in public health · 2024Review
- Chance Favors the Prepared Genomes: Horizontal Transfer Shapes the Emergence of Antibiotic Resistance Mutations in Core Genes.Molecular biology and evolution · 2023Article
- An Amino Acid Substitution in Elongation Factor EF-G1A Alters the Antibiotic Susceptibility of Pseudomonas aeruginosa LasR-Null Mutants.Journal of bacteriology · 2023Article
- Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a 2023 TBnet/RESIST-TB consensus statement.The Lancet. Infectious diseases · 2023Review
- Trends and challenges of multi-drug resistance in childhood tuberculosis.Frontiers in cellular and infection microbiology · 2023Review
- c-di-AMP signaling plays important role in determining antibiotic tolerance phenotypes of Mycobacterium smegmatis.Scientific reports · 2022Article
- Experimental Confirmation that an UncommonAntimicrobial agents and chemotherapy · 2022Article
- Mutation bias shapes the spectrum of adaptive substitutions.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The evolving biology ofFrontiers in cellular and infection microbiology · 2022Review
- The within-host evolution of antimicrobial resistance in Mycobacterium tuberculosis.FEMS microbiology reviews · 2021Review
- Article
- Genomic and Transcriptomic Analysis of BovineFrontiers in veterinary science · 2021Article
- Evolution of Drug-ResistantFrontiers in microbiology · 2021Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
Abstract
BACKGROUND AND
objectivesMultidrug resistant (MDR) bacteria are a growing threat to global health. Studies focusing on single antibiotics have shown that drug resistance is often associated with a fitness cost in the absence of drug. However, little is known about the fitness cost associated with resistance to multiple antibiotics. METHODOLOGY: We used Mycobacterium smegmatis as a model for human tuberculosis (TB) and an in vitro competitive fitness assay to explore the combined fitness effects and interaction between mutations conferring resistance to rifampicin (RIF) and ofloxacin (OFX); two of the most important first- and second-line anti-TB drugs, respectively.
resultsWe found that 4 out of 17 M. smegmatis mutants (24%) resistant to RIF and OFX showed a statistically significantly higher or lower competitive fitness than expected when assuming a multiplicative model of fitness effects of each individual mutation. Moreover, 6 out of the 17 double drug-resistant mutants (35%) had a significantly higher fitness than at least one of the corresponding single drug-resistant mutants. The particular combinations of resistance mutations associated with no fitness deficit in M. smegmatis were the most frequent among 151 clinical isolates of MDR and extensively drug-resistant (XDR) Mycobacterium tuberculosis from South Africa. CONCLUSIONS AND IMPLICATIONS: Our results suggest that epistasis between drug resistance mutations in mycobacteria can lead to MDR strains with no fitness deficit, and that these strains are positively selected in settings with a high burden of drug-resistant TB. Taken together, our findings support a role for epistasis in the evolution and epidemiology of MDR- and XDR-TB.
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