ArticlePLoS biology2021
The novel anti-CRISPR AcrIIA22 relieves DNA torsion in target plasmids and impairs SpyCas9 activity.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Review
- Mechanism of Cas9 inhibition by AcrIIA11.Nucleic acids research · 2025Article
- Dynamic basis of supercoiling-dependent DNA interrogation by Cas12a via R-loop intermediates.Nature communications · 2025Article
- Versatile plant genome engineering using anti-CRISPR-Cas12a systems.Science China. Life sciences · 2024Article
- Inhibitors of bacterial immune systems: discovery, mechanisms and applications.Nature reviews. Genetics · 2024Review
- CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023Review
- AcrIIC4 inhibits type II-C Cas9 by preventing R-loop formation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Dynamic interplay between target search and recognition for a Type I CRISPR-Cas system.Nature communications · 2023Article
- In Silico Approaches for Prediction of Anti-CRISPR Proteins.Journal of molecular biology · 2023Review
- Anti-CRISPR Discovery: Using Magnets to Find Needles in Haystacks.Journal of molecular biology · 2023Review
- Conjugation's Toolkit: the Roles of Nonstructural Proteins in Bacterial Sex.Journal of bacteriology · 2023Review
- Bacteriophage strategies for overcoming host antiviral immunity.Frontiers in microbiology · 2023Review
- A phage parasite deploys a nicking nuclease effector to inhibit viral host replication.Nucleic acids research · 2022Article
- Discovery of potent and versatile CRISPR-Cas9 inhibitors engineered for chemically controllable genome editing.Nucleic acids research · 2022Article
- Inhibition mechanisms of CRISPR-Cas9 by AcrIIA17 and AcrIIA18.Nucleic acids research · 2022Article
- Structure-based functional mechanisms and biotechnology applications of anti-CRISPR proteins.Nature reviews. Molecular cell biology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
To overcome CRISPR-Cas defense systems, many phages and mobile genetic elements (MGEs) encode CRISPR-Cas inhibitors called anti-CRISPRs (Acrs). Nearly all characterized Acrs directly bind Cas proteins to inactivate CRISPR immunity. Here, using functional metagenomic selection, we describe AcrIIA22, an unconventional Acr found in hypervariable genomic regions of clostridial bacteria and their prophages from human gut microbiomes. AcrIIA22 does not bind strongly to SpyCas9 but nonetheless potently inhibits its activity against plasmids. To gain insight into its mechanism, we obtained an X-ray crystal structure of AcrIIA22, which revealed homology to PC4-like nucleic acid-binding proteins. Based on mutational analyses and functional assays, we deduced that acrIIA22 encodes a DNA nickase that relieves torsional stress in supercoiled plasmids. This may render them less susceptible to SpyCas9, which uses free energy from negative supercoils to form stable R-loops. Modifying DNA topology may provide an additional route to CRISPR-Cas resistance in phages and MGEs.
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