ArticleProceedings. Biological sciences2015
Bypass of genetic constraints during mutator evolution to antibiotic resistance.
Article in Proceedings. Biological sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 83 citations in OpenAlex.
- Modelling the role of the microbiome in antimicrobial resistance across scales.Nature microbiology · 2026Review
- Resistance potentiators: Evolutionary catalysts of antibiotic resistance.PLoS biology · 2026Article
- Mutation-biased adaptation is consequential even in large bacterial populations.Nature communications · 2026Article
- Plasmid mutation rates scale with copy number.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Antimutator and Mutational Spectrum Effects Can Combine to Reduce Evolutionary Potential in Escherichia coli ΔnudJ.Molecular biology and evolution · 2025Article
- Mutation bias alters the distribution of fitness effects of mutations.PLoS biology · 2025Article
- Extending evolutionary forecasts across bacterial species.Proceedings. Biological sciences · 2024Article
- Mutation bias and adaptation in bacteria.Microbiology (Reading, England) · 2023Review
- Article
- Mutation bias and the predictability of evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Transient mutation bias increases the predictability of evolution on an empirical genotype-phenotype landscape.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Mutation bias shapes the spectrum of adaptive substitutions.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The within-host evolution of antimicrobial resistance in Mycobacterium tuberculosis.FEMS microbiology reviews · 2021Review
- Beyond horizontal gene transfer: the role of plasmids in bacterial evolution.Nature reviews. Microbiology · 2021Review
- Clinically relevant mutations in core metabolic genes confer antibiotic resistance.Science (New York, N.Y.) · 2021Article
- Mutation bias can shape adaptation in large asexual populations experiencing clonal interference.Proceedings. Biological sciences · 2020Article
- Non-lethal exposure to H2O2 boosts bacterial survival and evolvability against oxidative stress.PLoS genetics · 2020Article
- Genetic Paths to Evolutionary Rescue and the Distribution of Fitness Effects Along Them.Genetics · 2020Article
- The role of mutation bias in adaptive molecular evolution: insights from convergent changes in protein function.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Article
- Transition bias influences the evolution of antibiotic resistance in Mycobacterium tuberculosis.PLoS biology · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic constraints can block many mutational pathways to optimal genotypes in real fitness landscapes, yet the extent to which this can limit evolution remains to be determined. Interestingly, mutator bacteria elevate only specific types of mutations, and therefore could be very sensitive to genetic constraints. Testing this possibility is not only clinically relevant, but can also inform about the general impact of genetic constraints in adaptation. Here, we evolved 576 populations of two mutator and one wild-type Escherichia coli to doubling concentrations of the antibiotic cefotaxime. All strains carried TEM-1, a β-lactamase enzyme well known by its low availability of mutational pathways. Crucially, one of the mutators does not elevate any of the relevant first-step mutations known to improve cefatoximase activity. Despite this, both mutators displayed a similar ability to evolve more than 1000-fold resistance. Initial adaptation proceeded in parallel through general multi-drug resistance mechanisms. High-level resistance, in contrast, was achieved through divergent paths; with the a priori inferior mutator exploiting alternative mutational pathways in PBP3, the target of the antibiotic. These results have implications for mutator management in clinical infections and, more generally, illustrate that limits to natural selection in real organisms are alleviated by the existence of multiple loci contributing to fitness.
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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.