ArticlePloS one2014
CRISPR/Cas9-mediated phage resistance is not impeded by the DNA modifications of phage T4.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Article
- A pentose, as a cytosine nucleobase modification inApplied and environmental microbiology · 2026Article
- Distinct Phage-Encoded Enzymes for Substitution of Deoxythymidine by Deoxyuridine in Phage Genomes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Genetic manipulation of bacteriophage T4 utilizing the CRISPR-Cas13b system.Frontiers in genome editing · 2024Article
- Functional genomics of the lactic acid bacteriumHeliyon · 2022Article
- Article
- Discovery of potent and versatile CRISPR-Cas9 inhibitors engineered for chemically controllable genome editing.Nucleic acids research · 2022Article
- Hypermodified DNA in Viruses of E. coli and Salmonella.EcoSal Plus · 2021Review
- Risk Mitigation of Immunogenicity: A Key to Personalized Retinal Gene Therapy.International journal of molecular sciences · 2021Review
- The molecular basis for recognition of 5'-NNNCC-3' PAM and its methylation state by Acidothermus cellulolyticus Cas9.Nature communications · 2020Article
- Covalent Modifications of the Bacteriophage Genome Confer a Degree of Resistance to Bacterial CRISPR Systems.Journal of virology · 2020Article
- Optimization of T4 phage engineering via CRISPR/Cas9.Scientific reports · 2020Article
- Article
- Keeping crispr in check: diverse mechanisms of phage-encoded anti-crisprs.FEMS microbiology letters · 2019Review
- Identification and biosynthesis of thymidine hypermodifications in the genomic DNA of widespread bacterial viruses.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Bacteriophage DNA glucosylation impairs target DNA binding by type I and II but not by type V CRISPR-Cas effector complexes.Nucleic acids research · 2018Article
- Article
- Engineering of Bacteriophage T4 Genome Using CRISPR-Cas9.ACS synthetic biology · 2017Article
- The Discovery, Mechanisms, and Evolutionary Impact of Anti-CRISPRs.Annual review of virology · 2017Review
- The action of Escherichia coli CRISPR-Cas system on lytic bacteriophages with different lifestyles and development strategies.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Bacteria rely on two known DNA-level defenses against their bacteriophage predators: restriction-modification and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated (Cas) systems. Certain phages have evolved countermeasures that are known to block endonucleases. For example, phage T4 not only adds hydroxymethyl groups to all of its cytosines, but also glucosylates them, a strategy that defeats almost all restriction enzymes. We sought to determine whether these DNA modifications can similarly impede CRISPR-based defenses. In a bioinformatics search, we found naturally occurring CRISPR spacers that potentially target phages known to modify their DNA. Experimentally, we show that the Cas9 nuclease from the Type II CRISPR system of Streptococcus pyogenes can overcome a variety of DNA modifications in Escherichia coli. The levels of Cas9-mediated phage resistance to bacteriophage T4 and the mutant phage T4 gt, which contains hydroxymethylated but not glucosylated cytosines, were comparable to phages with unmodified cytosines, T7 and the T4-like phage RB49. Our results demonstrate that Cas9 is not impeded by N6-methyladenine, 5-methylcytosine, 5-hydroxymethylated cytosine, or glucosylated 5-hydroxymethylated cytosine.
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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.