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Widespread anti-CRISPR proteins in virulent bacteriophages inhibit a range of Cas9 proteins

Author

Listed:
  • Alexander P. Hynes

    (Université Laval
    McMaster University)

  • Geneviève M. Rousseau

    (Université Laval)

  • Daniel Agudelo

    (Université Laval)

  • Adeline Goulet

    (Aix-Marseille Université, Campus de Luminy
    Campus de Luminy)

  • Beatrice Amigues

    (Aix-Marseille Université, Campus de Luminy
    Campus de Luminy)

  • Jeremy Loehr

    (Université Laval)

  • Dennis A. Romero

    (DuPont Nutrition and Health)

  • Christophe Fremaux

    (DuPont Nutrition and Health)

  • Philippe Horvath

    (DuPont Nutrition and Health)

  • Yannick Doyon

    (Université Laval)

  • Christian Cambillau

    (Aix-Marseille Université, Campus de Luminy
    Campus de Luminy)

  • Sylvain Moineau

    (Université Laval
    Félix d’Hérelle Reference Center for Bacterial Viruses, Faculté de médecine dentaire, Université Laval)

Abstract

CRISPR-Cas systems are bacterial anti-viral systems, and bacterial viruses (bacteriophages, phages) can carry anti-CRISPR (Acr) proteins to evade that immunity. Acrs can also fine-tune the activity of CRISPR-based genome-editing tools. While Acrs are prevalent in phages capable of lying dormant in a CRISPR-carrying host, their orthologs have been observed only infrequently in virulent phages. Here we identify AcrIIA6, an Acr encoded in 33% of virulent Streptococcus thermophilus phage genomes. The X-ray structure of AcrIIA6 displays some features unique to this Acr family. We compare the activity of AcrIIA6 to those of other Acrs, including AcrIIA5 (also from S. thermophilus phages), and characterize their effectiveness against a range of CRISPR-Cas systems. Finally, we demonstrate that both Acr families from S. thermophilus phages inhibit Cas9-mediated genome editing of human cells.

Suggested Citation

  • Alexander P. Hynes & Geneviève M. Rousseau & Daniel Agudelo & Adeline Goulet & Beatrice Amigues & Jeremy Loehr & Dennis A. Romero & Christophe Fremaux & Philippe Horvath & Yannick Doyon & Christian Ca, 2018. "Widespread anti-CRISPR proteins in virulent bacteriophages inhibit a range of Cas9 proteins," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05092-w
    DOI: 10.1038/s41467-018-05092-w
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    Cited by:

    1. Lingguang Yang & Laixing Zhang & Peipei Yin & Hao Ding & Yu Xiao & Jianwei Zeng & Wenhe Wang & Huan Zhou & Qisheng Wang & Yi Zhang & Zeliang Chen & Maojun Yang & Yue Feng, 2022. "Insights into the inhibition of type I-F CRISPR-Cas system by a multifunctional anti-CRISPR protein AcrIF24," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Xieshuting Deng & Wei Sun & Xueyan Li & Jiuyu Wang & Zhi Cheng & Gang Sheng & Yanli Wang, 2024. "An anti-CRISPR that represses its own transcription while blocking Cas9-target DNA binding," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Cécile Philippe & Carlee Morency & Pier-Luc Plante & Edwige Zufferey & Rodrigo Achigar & Denise M. Tremblay & Geneviève M. Rousseau & Adeline Goulet & Sylvain Moineau, 2022. "A truncated anti-CRISPR protein prevents spacer acquisition but not interference," Nature Communications, Nature, vol. 13(1), pages 1-8, December.

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