ArticlePLoS biology2017
Multidrug-resistant bacteria compensate for the epistasis between resistances.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 78 citations in OpenAlex.
- Function-specific epistasis shapes evolutionary trajectories towards antibiotic resistance.Nature communications · 2026Article
- Epistasis and co-adaptation in bacterial genome evolution.Nature reviews. Genetics · 2026Review
- Antibiotic resistance among Gram-negative bacteria in bloodstream infections in Shiraz, Iran (2012-2023).AMB Express · 2026Article
- Advances in Double-Stranded DNA Targeting Technologies.Exploration (Beijing, China) · 2026Review
- 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
- Molecular characterization of drug-resistance genes and dynamics of multidrug-resistant Salmonella spp. in waterfowl: a pre- and post-antibiotic ban surveillance in Guangdong, China from 2013 to 2023.BMC microbiology · 2025Article
- Feature selection and aggregation for antibiotic resistance GWAS inFrontiers in microbiology · 2025Article
- Review
- Nano-Reactors Based on Ovotransferrin Organic Skeleton through a Ferroptosis-like Strategy Efficiently Enhance Antibacterial Activity.Journal of functional biomaterials · 2024Article
- Prunin Laurate Derived from Natural Substances Shows Antibacterial Activity against the Periodontal PathogenFoods (Basel, Switzerland) · 2024Article
- Costs of antibiotic resistance genes depend on host strain and environment and can influence community composition.Proceedings. Biological sciences · 2024Article
- The evolution of resistance to synergistic multi-drug combinations is more complex than evolving resistance to each individual drug component.Evolutionary applications · 2023Article
- Steering and controlling evolution - from bioengineering to fighting pathogens.Nature reviews. Genetics · 2023Review
- Chance Favors the Prepared Genomes: Horizontal Transfer Shapes the Emergence of Antibiotic Resistance Mutations in Core Genes.Molecular biology and evolution · 2023Article
- Epistasis decreases with increasing antibiotic pressure but not temperature.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- The relative transmission fitness of multidrug-resistant Mycobacterium tuberculosis in a drug resistance hotspot.Nature communications · 2023Article
- Reporting off-target effects of recombinant engineering using the pORTMAGE system.Journal of microbiological methods · 2023Article
- Using a combination of short- and long-read sequencing to investigate the diversity in plasmid- and chromosomally encoded extended-spectrum beta-lactamases (ESBLs) in clinicalMicrobial genomics · 2023Article
- Extensively Drug-Resistant Klebsiella pneumoniae Counteracts Fitness and Virulence Costs That Accompanied Ceftazidime-Avibactam Resistance Acquisition.Microbiology spectrum · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations conferring resistance to antibiotics are typically costly in the absence of the drug, but bacteria can reduce this cost by acquiring compensatory mutations. Thus, the rate of acquisition of compensatory mutations and their effects are key for the maintenance and dissemination of antibiotic resistances. While compensation for single resistances has been extensively studied, compensatory evolution of multiresistant bacteria remains unexplored. Importantly, since resistance mutations often interact epistatically, compensation of multiresistant bacteria may significantly differ from that of single-resistant strains. We used experimental evolution, next-generation sequencing, in silico simulations, and genome editing to compare the compensatory process of a streptomycin and rifampicin double-resistant Escherichia coli with those of single-resistant clones. We demonstrate that low-fitness double-resistant bacteria compensate faster than single-resistant strains due to the acquisition of compensatory mutations with larger effects. Strikingly, we identified mutations that only compensate for double resistance, being neutral or deleterious in sensitive or single-resistant backgrounds. Moreover, we show that their beneficial effects strongly decrease or disappear in conditions where the epistatic interaction between resistance alleles is absent, demonstrating that these mutations compensate for the epistasis. In summary, our data indicate that epistatic interactions between antibiotic resistances, leading to large fitness costs, possibly open alternative paths for rapid compensatory evolution, thereby potentially stabilizing costly multiple resistances in bacterial populations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.