CRISPR-repressed toxin-antitoxin provides herd immunity against anti-CRISPR elements.

Nat Chem Biol

Department of Microbial Physiological & Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

Published: July 2024

AI Article Synopsis

  • Prokaryotic CRISPR-Cas systems face threats from phage-encoded anti-CRISPR (Acr) factors, compromising their defense mechanisms.
  • Researchers discovered a phage-derived toxic protein that acts as a broad-spectrum anti-anti-CRISPR strategy, halting cell division when CRISPR-Cas effectors are inhibited.
  • This mechanism not only helps expel Acr elements from bacterial populations but also enables the identification of specific Acr proteins that enhance CRISPR efficiency against non-target DNA, suggesting CRISPR-Cas systems may provide a form of herd immunity against genetic invaders.

Article Abstract

Prokaryotic clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems are highly vulnerable to phage-encoded anti-CRISPR (Acr) factors. How CRISPR-Cas systems protect themselves remains unclear. Here we uncovered a broad-spectrum anti-anti-CRISPR strategy involving a phage-derived toxic protein. Transcription of this toxin is normally repressed by the CRISPR-Cas effector but is activated to halt cell division when the effector is inhibited by any anti-CRISPR proteins or RNAs. We showed that this abortive infection-like effect efficiently expels Acr elements from bacterial population. Furthermore, we exploited this anti-anti-CRISPR mechanism to develop a screening method for specific Acr candidates for a CRISPR-Cas system and successfully identified two distinct Acr proteins that enhance the binding of CRISPR effector to nontarget DNA. Our data highlight the broad-spectrum role of CRISPR-repressed toxins in counteracting various types of Acr factors. We propose that the regulatory function of CRISPR-Cas confers host cells herd immunity against Acr-encoding genetic invaders whether they are CRISPR targeted or not.

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Source
http://dx.doi.org/10.1038/s41589-024-01693-3DOI Listing

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