ArticleProceedings of the National Academy of Sciences of the United States of America2012
On the rapidity of antibiotic resistance evolution facilitated by a concentration gradient.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 208 citations in OpenAlex.
- Programmable 3D Microfluidics Reveals Motility-Driven Antibiotic Resistance Evolution in Gradients.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Environment heterogeneity creates fast amplifiers of natural selection in graph-structured populations.Nature communications · 2026Article
- Gradient metapopulation microfluidic ecologies shape genetic and biofilm drivers of T4r phage resistance in E. coli.NPJ biofilms and microbiomes · 2026Article
- The effect of the fitness gradient on fixation probability.Nature communications · 2026Article
- Forecasting Multitrait Resistance Evolution under Antibiotic Stress.Molecular biology and evolution · 2026Article
- EnvZ/OmpR-driven cooperative behavior promotes cefiderocol resistance in a hanging-droplet evolution system.Science advances · 2026Article
- Slow spatial migration can help eradicate cooperative antimicrobial resistance in time-varying environments.PLoS computational biology · 2026Article
- Evolutionary drivers of divergent collateral sensitivity responses during antibiotic therapy.Nature ecology & evolution · 2026Review
- Linking spatial drug heterogeneity to microbial growth dynamics in theory and experiment.PLoS computational biology · 2026Article
- Higher levels of antibiotic resistance are less competitive: the hidden ecological cost of no-metabolic cost resistance.bioRxiv : the preprint server for biology · 2025Article
- Deciphering and steering population-level response under spatial drug heterogeneity on microhabitat structures.bioRxiv : the preprint server for biology · 2025Article
- Spatial structure facilitates evolutionary rescue by drug resistance.PLoS computational biology · 2025Article
- Spatial population dynamics of bacterial colonies with social antibiotic resistance.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Insights into antibiotic resistance promoted by quinolone exposure.Antimicrobial agents and chemotherapy · 2025Article
- Microbial culture vs. mNGS: diagnostic variations in periprosthetic joint infection.Frontiers in cellular and infection microbiology · 2025Article
- Genome alteration of Leishmania orientalis under Amphotericin B inhibiting conditions.PLoS neglected tropical diseases · 2024Article
- Mutant fate in spatially structured populations on graphs: Connecting models to experiments.PLoS computational biology · 2024Article
- A 'rich-get-richer' mechanism drives patchy dynamics and resistance evolution in antibiotic-treated bacteria.Molecular systems biology · 2024Article
- Microfluidic Ecology Unravels the Genetic and Ecological Drivers of T4r Bacteriophage Resistance in E. coli: Insights into Biofilm-Mediated Evolution.Research square · 2024Article
- Modeling spatial evolution of multi-drug resistance under drug environmental gradients.PLoS computational biology · 2024Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The rapid emergence of bacterial strains resistant to multiple antibiotics is posing a growing public health risk. The mechanisms underlying the rapid evolution of drug resistance are, however, poorly understood. The heterogeneity of the environments in which bacteria encounter antibiotic drugs could play an important role. E.g., in the highly compartmentalized human body, drug levels can vary substantially between different organs and tissues. It has been proposed that this could facilitate the selection of resistant mutants, and recent experiments support this. To study the role of spatial heterogeneity in the evolution of drug resistance, we present a quantitative model describing an environment subdivided into relatively isolated compartments with various antibiotic concentrations, in which bacteria evolve under the stochastic processes of proliferation, migration, mutation and death. Analytical and numerical results demonstrate that concentration gradients can foster a mode of adaptation that is impossible in uniform environments. It allows resistant mutants to evade competition and circumvent the slow process of fixation by invading compartments with higher drug concentrations, where less resistant strains cannot subsist. The speed of this process increases sharply with the sensitivity of the growth rate to the antibiotic concentration, which we argue to be generic. Comparable adaptation rates in uniform environments would require a high selection coefficient (s > 0.1) for each forward mutation. Similar processes can occur if the heterogeneity is more complex than just a linear gradient. The model may also be applicable to other adaptive processes involving environmental heterogeneity and range expansion.
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Registered trials
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.