ArticleProceedings of the National Academy of Sciences of the United States of America2021
Coevolutionary phage training leads to greater bacterial suppression and delays the evolution of phage resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed.
- Experimental evolution of phage K enhances antibacterial activity against USA300 MRSA in lung infection models.Emerging microbes & infections · 2026Article
- Phylogeny-agnostic strain-level prediction of phage-host interactions from genomes using machine learning.Nature microbiology · 2026Article
- Modeling Phage-Antibiotic Synergy, Innate Immunity, and Phage Resistance in Multidrug-ResistantAntibiotics (Basel, Switzerland) · 2026Article
- Capsular Polysaccharide Safeguards a Prophage-Bacterium Symbiosis by Preventing Collateral Attack and Promoting Viral Transmission.bioRxiv : the preprint server for biology · 2026Article
- Parallel evolution of chimeric genes in microbial evolution experiments.Microbial genomics · 2026Article
- Phage therapy: from basic biology to clinical application.Nature reviews. Microbiology · 2026Review
- WaaL-WaaP receptor cross-talk drives phage-induced collateral sensitivity to colistin in Salmonella Pullorum.Veterinary research · 2026Article
- Mechanisms of Resistance, Insights From Case Reports, and Future Prospects in Mycobacteriophage Therapy.Journal of the Royal Society of New Zealand · 2026Review
- Phage host range: determinants, dynamics and applications.Nature reviews. Microbiology · 2026Review
- Directed evolution of phage Romulus in biofilm-embeddedBiofilm · 2026Article
- A qPCR-Based Screening Platform for Exploratory Assessment of Phage Training Outcomes inViruses · 2026Article
- CApEsid biOfilm: a suggested pipeline for clinical phage microbiology for biofilm infections based on comparative method study.Scientific reports · 2026Article
- From hype to hope: reanimating phage therapy through evidence-based multidisciplinarity.Nature communications · 2026Review
- Sequential Phage Delivery Can Outperform Cocktails by Delaying Cross-Resistance Evolution.Viruses · 2026Article
- High-resolution phage-host assignment through key proteins using large language models.Nature communications · 2026Article
- Expanding the Antimicrobial Toolbox with Therapeutic Viruses: Mechanisms, Pharmaceutical Formulation, and Translational Outlook.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Phase variation inEngineering microbiology · 2026Article
- Modeling the Phage Properties Best for Therapy.Viruses · 2026Article
- 3D Printing of Bacteriophage-Loaded Hydrogels: Development of a Local and Long-Lasting Delivery System.Advanced healthcare materials · 2026Article
- Phage-Based Approaches to ChronicAntibiotics (Basel, Switzerland) · 2026Review
62 more citing papers are in PubMed but not listed here.
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5 authors.
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Abstract
The evolution of antibiotic-resistant bacteria threatens to become the leading cause of worldwide mortality. This crisis has renewed interest in the practice of phage therapy. Yet, bacteria's capacity to evolve resistance may debilitate this therapy as well. To combat the evolution of phage resistance and improve treatment outcomes, many suggest leveraging phages' ability to counter resistance by evolving phages on target hosts before using them in therapy (phage training). We found that in vitro, λtrn, a phage trained for 28 d, suppressed bacteria ∼1,000-fold for three to eight times longer than its untrained ancestor. Prolonged suppression was due to a delay in the evolution of resistance caused by several factors. Mutations that confer resistance to λtrn are ∼100× less common, and while the target bacterium can evolve complete resistance to the untrained phage in a single step, multiple mutations are required to evolve complete resistance to λtrn. Mutations that confer resistance to λtrn are more costly than mutations for untrained phage resistance. Furthermore, when resistance does evolve, λtrn is better able to suppress these forms of resistance. One way that λtrn improved was through recombination with a gene in a defunct prophage in the host genome, which doubled phage fitness. This transfer of information from the host genome is an unexpected but highly efficient mode of training phage. Lastly, we found that many other independently trained λ phages were able to suppress bacterial populations, supporting the important role training could play during phage therapeutic development.
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