ArticlePLoS genetics2016
P1 Ref Endonuclease: A Molecular Mechanism for Phage-Enhanced Antibiotic Lethality.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
24 citing papers in PubMed, 32 citations in OpenAlex.
- The Oxidative DNA Lesion 6-Oxo-M1dG is a Potent Replication Block, Inducing Deletions and Base Substitution Mutations In Vivo.Chemical research in toxicology · 2026Article
- Topoisomerase III limits RecA-dependent DNA amplification in the chromosome terminus with RecG.Nucleic acids research · 2026Article
- Bacteriophage deploys a RecA-dependent nuclease to inhibit Staphylococcus aureus replication and promote phage propagation.Nucleic acids research · 2026Article
- Phage-quinolone synergy: mechanisms, clinical strategies, and translational prospects.Frontiers in microbiology · 2026Review
- Synergy between ciprofloxacin and temperate phages overcomes therapeutic limitations caused by lysogen formation.Scientific reports · 2025Article
- Characterization and genomics of phage Henu2_3 against K1 Klebsiella pneumoniae and its efficacy in animal models.AMB Express · 2025Article
- The virulent bacteriophage Henu8 as an antimicrobial synergist againstMicrobiology spectrum · 2025Article
- Phage (cocktail)-antibiotic synergism: a new frontier in addressingFrontiers in microbiology · 2025Article
- A Comprehensive Review on Phage Therapy and Phage-Based Drug Development.Antibiotics (Basel, Switzerland) · 2024Review
- Characterization and genomic analysis of the first Oceanospirillum phage, vB_OliS_GJ44, representing a novel siphoviral cluster.BMC genomics · 2021Article
- Bacteriophage Technology and Modern Medicine.Antibiotics (Basel, Switzerland) · 2021Review
- Advances in Phage Therapy: Targeting theViruses · 2021Review
- Characterization of a Novel Bacteriophage Henu2 and Evaluation of the Synergistic Antibacterial Activity of Phage-Antibiotics.Antibiotics (Basel, Switzerland) · 2021Article
- Moxifloxacin Activates the SOS Response inMicroorganisms · 2021Article
- Single-molecule live-cell imaging reveals RecB-dependent function of DNA polymerase IV in double strand break repair.Nucleic acids research · 2020Article
- Interaction with single-stranded DNA-binding protein localizes ribonuclease HI to DNA replication forks and facilitates R-loop removal.Molecular microbiology · 2020Article
- RecFOR epistasis group: RecF and RecO have distinct localizations and functions in Escherichia coli.Nucleic acids research · 2019Article
- Phage Therapy in the Postantibiotic Era.Clinical microbiology reviews · 2019Review
- Overexpression of AmpC Promotes Bacteriophage Lysis of Ampicillin-ResistantFrontiers in microbiology · 2019Article
- Phage-Antibiotic Synergy via Delayed Lysis.Applied and environmental microbiology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ref is an HNH superfamily endonuclease that only cleaves DNA to which RecA protein is bound. The enigmatic physiological function of this unusual enzyme is defined here. Lysogenization by bacteriophage P1 renders E. coli more sensitive to the DNA-damaging antibiotic ciprofloxacin, an example of a phenomenon termed phage-antibiotic synergy (PAS). The complementary effect of phage P1 is uniquely traced to the P1-encoded gene ref. Ref is a P1 function that amplifies the lytic cycle under conditions when the bacterial SOS response is induced due to DNA damage. The effect of Ref is multifaceted. DNA binding by Ref interferes with normal DNA metabolism, and the nuclease activity of Ref enhances genome degradation. Ref also inhibits cell division independently of the SOS response. Ref gene expression is toxic to E. coli in the absence of other P1 functions, both alone and in combination with antibiotics. The RecA proteins of human pathogens Neisseria gonorrhoeae and Staphylococcus aureus serve as cofactors for Ref-mediated DNA cleavage. Ref is especially toxic during the bacterial SOS response and the limited growth of stationary phase cultures, targeting aspects of bacterial physiology that are closely associated with the development of bacterial pathogen persistence.
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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.