Bacterial alginate regulators and phage homologs repress CRISPR-Cas immunity

Nat Microbiol. 2020 May;5(5):679-687. doi: 10.1038/s41564-020-0691-3. Epub 2020 Mar 23.

Abstract

CRISPR-Cas systems are adaptive immune systems that protect bacteria from bacteriophage (phage) infection1. To provide immunity, RNA-guided protein surveillance complexes recognize foreign nucleic acids, triggering their destruction by Cas nucleases2. While the essential requirements for immune activity are well understood, the physiological cues that regulate CRISPR-Cas expression are not. Here, a forward genetic screen identifies a two-component system (KinB-AlgB), previously characterized in the regulation of Pseudomonas aeruginosa alginate biosynthesis3,4, as a regulator of the expression and activity of the P. aeruginosa Type I-F CRISPR-Cas system. Downstream of KinB-AlgB, activators of alginate production AlgU (a σE orthologue) and AlgR repress CRISPR-Cas activity during planktonic and surface-associated growth5. AmrZ, another alginate regulator6, is triggered to repress CRISPR-Cas immunity upon surface association. Pseudomonas phages and plasmids have taken advantage of this regulatory scheme and carry hijacked homologs of AmrZ that repress CRISPR-Cas expression and activity. This suggests that while CRISPR-Cas regulation may be important to limit self-toxicity, endogenous repressive pathways represent a vulnerability for parasite manipulation.

Publication types

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

MeSH terms

  • Alginates / metabolism*
  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bacteria / virology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacteriophages / genetics*
  • Base Sequence
  • CRISPR-Cas Systems
  • Clustered Regularly Interspaced Short Palindromic Repeats*
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Bacterial
  • Genes, Bacterial / genetics
  • Genes, Regulator / genetics
  • Immunity
  • Pseudomonas Phages / genetics
  • Pseudomonas aeruginosa / metabolism
  • Transcription Factors
  • Transcription, Genetic

Substances

  • Alginates
  • Bacterial Proteins
  • DNA-Binding Proteins
  • Transcription Factors