Anti-CRISPR-Associated Proteins Are Crucial Repressors of Anti-CRISPR Transcription

Cell. 2019 Sep 5;178(6):1452-1464.e13. doi: 10.1016/j.cell.2019.07.046. Epub 2019 Aug 29.


Phages express anti-CRISPR (Acr) proteins to inhibit CRISPR-Cas systems that would otherwise destroy their genomes. Most acr genes are located adjacent to anti-CRISPR-associated (aca) genes, which encode proteins with a helix-turn-helix DNA-binding motif. The conservation of aca genes has served as a signpost for the identification of acr genes, but the function of the proteins encoded by these genes has not been investigated. Here we reveal that an acr-associated promoter drives high levels of acr transcription immediately after phage DNA injection and that Aca proteins subsequently repress this transcription. Without Aca activity, this strong transcription is lethal to a phage. Our results demonstrate how sufficient levels of Acr proteins accumulate early in the infection process to inhibit existing CRISPR-Cas complexes in the host cell. They also imply that the conserved role of Aca proteins is to mitigate the deleterious effects of strong constitutive transcription from acr promoters.

Keywords: CRISPR-Cas; Horizontal gene transfer; Phage; Pseudomonas aeruginosa; Transcriptional regulator; anti-CRISPR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteriophages / genetics*
  • CRISPR-Associated Proteins / genetics
  • CRISPR-Cas Systems / genetics*
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Escherichia coli / virology
  • Promoter Regions, Genetic / genetics
  • Pseudomonas aeruginosa / virology
  • Transcription Factors / genetics
  • Transcription, Genetic
  • Viral Proteins / genetics*


  • CRISPR-Associated Proteins
  • Transcription Factors
  • Viral Proteins