Discovery of widespread type I and type V CRISPR-Cas inhibitors

Science. 2018 Oct 12;362(6411):240-242. doi: 10.1126/science.aau5174. Epub 2018 Sep 6.

Abstract

Bacterial CRISPR-Cas systems protect their host from bacteriophages and other mobile genetic elements. Mobile elements, in turn, encode various anti-CRISPR (Acr) proteins to inhibit the immune function of CRISPR-Cas. To date, Acr proteins have been discovered for type I (subtypes I-D, I-E, and I-F) and type II (II-A and II-C) but not other CRISPR systems. Here, we report the discovery of 12 acr genes, including inhibitors of type V-A and I-C CRISPR systems. AcrVA1 inhibits a broad spectrum of Cas12a (Cpf1) orthologs-including MbCas12a, Mb3Cas12a, AsCas12a, and LbCas12a-when assayed in human cells. The acr genes reported here provide useful biotechnological tools and mark the discovery of acr loci in many bacteria and phages.

Publication types

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

MeSH terms

  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • CRISPR-Cas Systems*
  • Cell Line
  • Computational Biology / methods
  • Endonucleases / antagonists & inhibitors*
  • Gene Editing*
  • Humans
  • Moraxella / genetics*
  • Pseudomonas / genetics*

Substances

  • Bacterial Proteins
  • Cpf1 nuclease, Acidaminococcus
  • Endonucleases