Viral recombination systems limit CRISPR-Cas targeting through the generation of escape mutations

被引:12
|
作者
Hossain, Amer A. [1 ]
McGinn, Jon [1 ]
Meeske, Alexander J. [1 ]
Modell, Joshua W. [1 ,3 ]
Marraffini, Luciano A. [1 ,2 ]
机构
[1] Rockefeller Univ, Lab Bacteriol, 1230 York Ave, New York, NY 10065 USA
[2] Rockefeller Univ, Howard Hughes Med Inst, 1230 York Ave, New York, NY 10065 USA
[3] Johns Hopkins Univ, Dept Mol Biol & Genet, Sch Med, 725 N Wolfe St, Baltimore, MD 21205 USA
关键词
IN-VITRO RECONSTITUTION; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; RECBCD ENZYME; LEVEL EXPRESSION; RECA PROTEIN; DNA; RNA; IMMUNITY; CHI;
D O I
10.1016/j.chom.2021.09.001
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 lambda uses the Red system (gam-exo-bet) to promote recombination between related phages. Here, we show that lambda 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.
引用
收藏
页码:1482 / +
页数:26
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