ArticleApplied and environmental microbiology2012
Reversing bacterial resistance to antibiotics by phage-mediated delivery of dominant sensitive genes.
Article in Applied and environmental microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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103 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
- Positive epistasis among ribosomal mutations drives high-level streptomycin resistance inApplied and environmental microbiology · 2026Article
- Giving Antibiotics a Second Chance: Evolutionary Trade-Offs and Phage-Driven Restoration of Antibiotic Susceptibility.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
- Management of Diabetic Foot Infections Using Phage Therapy.Infection and drug resistance · 2026Review
- Pharmacological evaluation of phage-antibiotic synergism against clinical isolates of multi-drug resistant Staphylococcus aureus in a burn-induced infection mouse model.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2025Article
- Effects of bacteriophages on gut microbiome functionality.Gut microbes · 2025Review
- Advanced Strategies in Phage Research: Innovations, Applications, and Challenges.Microorganisms · 2025Review
- CRISPR-Cas10-Assisted Structural Modification of StaphylococcalACS synthetic biology · 2025Article
- The virulent bacteriophage Henu8 as an antimicrobial synergist againstMicrobiology spectrum · 2025Article
- Review
- Engineering bacteriophages for targeted superbug eradication.Molecular biology reports · 2025Review
- Engineering Phages to Fight Multidrug-Resistant Bacteria.Chemical reviews · 2025Review
- Hotspots of genetic change in Yersinia pestis.Nature communications · 2025Article
- Review
- Beyond Antibiotics: Exploring the Potential of Bacteriophages and Phage Therapy.PHAGE (New Rochelle, N.Y.) · 2024Review
- Isolation and Characterization of a Novel Jumbo Phage HPP-Temi InfectingAntibiotics (Basel, Switzerland) · 2024Article
- Review
- A Comprehensive Review on Phage Therapy and Phage-Based Drug Development.Antibiotics (Basel, Switzerland) · 2024Review
- The Potential of Phage Treatment to Inactivate Planktonic and Biofilm-FormingMicroorganisms · 2024Article
43 more citing papers are in PubMed but not listed here.
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4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pathogen resistance to antibiotics is a rapidly growing problem, leading to an urgent need for novel antimicrobial agents. Unfortunately, development of new antibiotics faces numerous obstacles, and a method that resensitizes pathogens to approved antibiotics therefore holds key advantages. We present a proof of principle for a system that restores antibiotic efficiency by reversing pathogen resistance. This system uses temperate phages to introduce, by lysogenization, the genes rpsL and gyrA conferring sensitivity in a dominant fashion to two antibiotics, streptomycin and nalidixic acid, respectively. Unique selective pressure is generated to enrich for bacteria that harbor the phages carrying the sensitizing constructs. This selection pressure is based on a toxic compound, tellurite, and therefore does not forfeit any antibiotic for the sensitization procedure. We further demonstrate a possible way of reducing undesirable recombination events by synthesizing dominant sensitive genes with major barriers to homologous recombination. Such synthesis does not significantly reduce the gene's sensitization ability. Unlike conventional bacteriophage therapy, the system does not rely on the phage's ability to kill pathogens in the infected host, but instead, on its ability to deliver genetic constructs into the bacteria and thus render them sensitive to antibiotics prior to host infection. We believe that transfer of the sensitizing cassette by the constructed phage will significantly enrich for antibiotic-treatable pathogens on hospital surfaces. Broad usage of the proposed system, in contrast to antibiotics and phage therapy, will potentially change the nature of nosocomial infections toward being more susceptible to antibiotics rather than more resistant.
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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.