ArticleProceedings of the National Academy of Sciences of the United States of America2008
Drug interactions modulate the potential for evolution of resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
What it found
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Who cites it
135 citing papers in PubMed, 219 citations in OpenAlex.
- Collateral sensitivity-harnessing microbial vulnerabilities as a solution to antimicrobial resistance.Molecular biology reports · 2026Review
- Beyond resistance and tolerance: rethinking evolutionary responses to antibiotics from the perspective of individual bacterial cells.Nature communications · 2026Review
- Article
- Evolutionary drivers of divergent collateral sensitivity responses during antibiotic therapy.Nature ecology & evolution · 2026Review
- Mechanisms of microbial community restructuring and metabolic pathway modulation during biological nitrogen removal in livestock wastewater under combined antibiotic stress.World journal of microbiology & biotechnology · 2026Article
- Linezolid and levofloxacin: an uncommon pairing that suppresses evolution of resistance inFEMS microbes · 2026Article
- Pulsed antibiotic release into the environment may foster the spread of antimicrobial resistance.FEMS microbiology ecology · 2025Article
- Antimicrobial potentials and challenges of paracetamol: A comprehensive reassessment based on database reports.Pharmaceutical science advances · 2025Review
- Environment-by-Environment Interactions Differ Across Genetic Backgrounds.Molecular biology and evolution · 2025Article
- Interactions within higher-order antibiotic combinations do not influence the rate of adaptation in bacteria.Evolution; international journal of organic evolution · 2025Article
- Dynamic collateral sensitivity profiles highlight opportunities and challenges for optimizing antibiotic treatments.PLoS biology · 2025Article
- Unlocking the potential of experimental evolution to study drug resistance in pathogenic fungi.npj antimicrobials and resistance · 2024Review
- In Vitro Synergistic Effect of Lefamulin with Doxycycline, Rifampin, and Quinupristin/Dalfopristin Against Enterococci.Microorganisms · 2024Article
- Antimicrobial Use Among Outpatients at Benjamin Mkapa Hospital in Dodoma Central Zone of Tanzania: A Prospective Descriptive Study.Infectious diseases & clinical microbiology · 2024Article
- Preserving the efficacy of antibiotics to tackle antibiotic resistance.Microbial biotechnology · 2024Review
- Article
- Synthesis of ciprofloxacin-linked 1,2,3-triazole conjugates as potent antibacterial agents using click chemistry: exploring their function as DNA gyrase inhibitorsRSC advances · 2024Article
- Wiring Between Close Nodes in Molecular Networks Evolves More Quickly Than Between Distant Nodes.Molecular biology and evolution · 2024Article
- Modeling spatial evolution of multi-drug resistance under drug environmental gradients.PLoS computational biology · 2024Article
- Susceptible bacteria can survive antibiotic treatment in the mammalian gastrointestinal tract without evolving resistance.Cell host & microbe · 2024Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Antimicrobial treatments increasingly rely on multidrug combinations, in part because of the emergence and spread of antibiotic resistance. The continued effectiveness of combination treatments depends crucially on the frequency with which multidrug resistance arises. Yet, it is unknown how this propensity for resistance depends on cross-resistance and on epistatic interactions-ranging from synergy to antagonism-between the drugs. Here, we analyzed how interactions between pairs of drugs affect the spontaneous emergence of resistance in the medically important pathogen Staphylococcus aureus. Resistance is selected for within a window of drug concentrations high enough to inhibit wild-type growth but low enough for some resistant mutants to grow. Introducing an experimental method for high-throughput colony imaging, we counted resistant colonies arising across a two-dimensional matrix of drug concentrations for each of three drug pairs. Our data show that these different drug combinations have significantly different impacts on the size of the window of drug concentrations where resistance is selected for. We framed these results in a mathematical model in which the frequencies of resistance to single drugs, cross-resistance, and epistasis combine to determine the propensity for multidrug resistance. The theory suggests that drug pairs which interact synergistically, preferred for their immediate efficacy, may in fact favor the future evolution of resistance. This framework reveals the central role of drug epistasis in the evolution of resistance and points to new strategies for combating the emergence of drug-resistant bacteria.
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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.