Discovery of multiple anti-CRISPRs highlights anti-defense gene clustering in mobile genetic elements

Rafael Pinilla-Redondo, Saadlee Shehreen, Nicole D Marino, Robert D Fagerlund, Chris M Brown, Søren J Sørensen, Peter C Fineran, Joseph Bondy-Denomy

Research output: Contribution to journalJournal articleResearchpeer-review


Many prokaryotes employ CRISPR-Cas systems to combat invading mobile genetic elements (MGEs). In response, some MGEs have developed strategies to bypass immunity, including anti-CRISPR (Acr) proteins; yet the diversity, distribution and spectrum of activity of this immune evasion strategy remain largely unknown. Here, we report the discovery of new Acrs by assaying candidate genes adjacent to a conserved Acr-associated (Aca) gene, aca5, against a panel of six type I systems: I-F (Pseudomonas, Pectobacterium, and Serratia), I-E (Pseudomonas and Serratia), and I-C (Pseudomonas). We uncover 11 type I-F and/or I-E anti-CRISPR genes encoded on chromosomal and extrachromosomal MGEs within Enterobacteriaceae and Pseudomonas, and an additional Aca (aca9). The acr genes not only associate with other acr genes, but also with genes encoding inhibitors of distinct bacterial defense systems. Thus, our findings highlight the potential exploitation of acr loci neighborhoods for the identification of previously undescribed anti-defense systems.

Original languageEnglish
JournalNature Communications
Issue number1
Pages (from-to)5652
Publication statusPublished - 6 Nov 2020


  • Bacteria/genetics
  • Bacterial Proteins/genetics
  • Bacteriophages/genetics
  • CRISPR-Cas Systems
  • Interspersed Repetitive Sequences
  • Multigene Family

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