Viral Recombination Systems Limit CRISPR-Cas Targeting Through the Generation of Escape Mutations
Overview
Microbiology
Affiliations
CRISPR-Cas systems provide immunity to bacteria by programing Cas nucleases with RNA guides that recognize and cleave infecting viral genomes. Bacteria and their viruses each encode recombination systems that could repair the cleaved viral DNA. However, it is unknown whether and how these systems can affect CRISPR immunity. Bacteriophage λ uses the Red system (gam-exo-bet) to promote recombination between related phages. Here, we show that λ Red also mediates evasion of CRISPR-Cas targeting. Gam inhibits the host E. coli RecBCD recombination system, allowing recombination and repair of the cleaved DNA by phage Exo-Beta, which promotes the generation of mutations within the CRISPR target sequence. Red recombination is strikingly more efficient than the host's RecBCD-RecA in the production of large numbers of phages that escape CRISPR targeting. These results reveal a role for Red-like systems in the protection of bacteriophages against sequence-specific nucleases, which may facilitate their spread across viral genomes.
SspA is a transcriptional regulator of CRISPR adaptation in E. coli.
Lopez S, Lee Y, Zhang K, Shipman S Nucleic Acids Res. 2024; 53(4).
PMID: 39727179 PMC: 11879090. DOI: 10.1093/nar/gkae1244.
Raza A, Fatima P, Yasmeen B, Rana Z, Ellakwa D Naunyn Schmiedebergs Arch Pharmacol. 2024; .
PMID: 39404843 DOI: 10.1007/s00210-024-03509-6.
Assessing the Role of Bacterial Innate and Adaptive Immunity as Barriers to Conjugative Plasmids.
Siedentop B, Losa Mediavilla C, Kouyos R, Bonhoeffer S, Chabas H Mol Biol Evol. 2024; 41(10).
PMID: 39382385 PMC: 11525042. DOI: 10.1093/molbev/msae207.
CRISPR-Cas9 target-strand nicking provides phage resistance by inhibiting replication.
Nguyen G, Schelling M, Sashital D bioRxiv. 2024; .
PMID: 39282300 PMC: 11398490. DOI: 10.1101/2024.09.05.611540.
CRISPR-Cas12a exhibits metal-dependent specificity switching.
Nguyen G, Schelling M, Raju A, Buscher K, Sritharan A, Sashital D Nucleic Acids Res. 2024; 52(16):9343-9359.
PMID: 39019776 PMC: 11381342. DOI: 10.1093/nar/gkae613.