ArticleeLife2021
Multi-step vs. single-step resistance evolution under different drugs, pharmacokinetics, and treatment regimens.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed.
- Simple birth-death-mutation models predict some-but not all-aspects of the experimental evolution of antibiotic resistance.PLoS computational biology · 2026Article
- SOS-mediated prophage induction constrains resistance evolution to DNA-damaging antibiotics.bioRxiv : the preprint server for biology · 2026Article
- Genome co-adaptation and the evolution of methicillin resistant Staphylococcus aureus.Genome biology · 2026Article
- Investigating the consequences of the mating system for drug resistance evolution inProceedings. Biological sciences · 2025Article
- Uncovering the genetic basis ofiScience · 2025Article
- Expanding horizons in theragnostics: from oncology to multidisciplinary applications.La Radiologia medica · 2025Review
- Dual Mutations inInternational journal of molecular sciences · 2025Article
- MIDAA: deep archetypal analysis for interpretable multi-omic data integration based on biological principles.Genome biology · 2025Article
- Targeting efflux pumps prevents the multi-step evolution of high-level resistance to fluoroquinolone inMicrobiology spectrum · 2025Article
- Spatial structure facilitates evolutionary rescue by drug resistance.PLoS computational biology · 2025Article
- Resistance profiles ofIranian journal of microbiology · 2025Article
- Quantitative analysis of relationship between mutation rate and speed of adaptation under antibiotic exposure in Escherichia coli.PLoS genetics · 2025Article
- Detection of Possible Resistance Mechanisms in UropathogenicBiomolecules · 2025Article
- Nanocomposite alginate hydrogel loaded with propranolol hydrochloride kolliphorDrug delivery and translational research · 2025Article
- Multiplicity of type 6 secretion system toxins limits the evolution of resistance.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Contrasting Dynamics of Intracellular and Extracellular Antibiotic Resistance Genes in Response to Nutrient Variations in Aquatic Environments.Antibiotics (Basel, Switzerland) · 2024Article
- In Vitro Resistance-Predicting Studies and In Vitro Resistance-Related Parameters-A Hit-to-Lead Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The many dimensions of combination therapy: How to combine antibiotics to limit resistance evolution.Evolutionary applications · 2024Article
- The evolution of antimicrobial peptide resistance in Pseudomonas aeruginosa is severely constrained by random peptide mixtures.PLoS biology · 2024Article
- Unveiling the Multifaceted Capabilities of EndophyticPharmaceuticals (Basel, Switzerland) · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The success of antimicrobial treatment is threatened by the evolution of drug resistance. Population genetic models are an important tool in mitigating that threat. However, most such models consider resistance emergence via a single mutational step. Here, we assembled experimental evidence that drug resistance evolution follows two patterns: (i) a single mutation, which provides a large resistance benefit, or (ii) multiple mutations, each conferring a small benefit, which combine to yield high-level resistance. Using stochastic modeling, we then investigated the consequences of these two patterns for treatment failure and population diversity under various treatments. We find that resistance evolution is substantially limited if more than two mutations are required and that the extent of this limitation depends on the combination of drug type and pharmacokinetic profile. Further, if multiple mutations are necessary, adaptive treatment, which only suppresses the bacterial population, delays treatment failure due to resistance for a longer time than aggressive treatment, which aims at eradication.
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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.