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PreprintCited by 144Bacteriophages and microbial interactionsCRISPR and Genetic EngineeringBacterial Genetics and Biotechnology

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Phages overcome bacterial immunity via diverse anti-defense proteins

Open access
Yirmiya, Erez, Leavitt, Azita, Lu, Allen, Avraham, Carmel, Osterman, Ilya, Garb, Jeremy, Antine, Sadie P., Mooney, Sarah E., Hobbs, Sam J., Kranzusch, Philip J., Amitai, Gil, Sorek, Rotem·2023·Nature
DOI 10.1101/2023.05.01.538930

Preprint — published as 10.1038/s41586-023-06869-w

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Abstract

It was recently shown that bacteria employ, apart from CRISPR-Cas and restriction systems, a considerable diversity of phage resistance systems, but it is largely unknown how phages cope with this multilayered bacterial immunity. Here, we analyzed groups of closely related Bacillus phages that showed differential sensitivity to bacterial defense systems, and identified multiple families of anti-defense proteins that inhibit the Gabija, Thoeris, and Hachiman systems. We show that these proteins efficiently cancel the defensive activity when co-expressed with the respective defense system or introduced into phage genomes. Homologs of these anti-defense proteins are found in hundreds of phages that infect taxonomically diverse bacterial species. We show that an anti-Gabija protein, denoted Gad1, blocks the ability of the Gabija defense complex to cleave phage-derived DNA. Our data further reveal an anti-Thoeris protein, denoted Tad2, which is a “sponge” that sequesters the immune signaling molecules produced by Thoeris TIR-domain proteins in response to phage. Our results demonstrate that phages encode an arsenal of anti-defense proteins that can disable a variety of bacterial defense mechanisms.

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Metadata

Authors
Yirmiya, E., Leavitt, A., Lu, A., Avraham, C., Osterman, I., Garb, J., Antine, S. P., Mooney, S. E., Hobbs, S. J., Kranzusch, P. J., Amitai, G., & Sorek, R.
Affiliations
  • Weizmann Institute of Science (IL)
  • Harvard University (US)
Corresponding author
  • Amitai, Gil
  • Sorek, Rotem
ORCID
Venue
Nature
Publisher
openRxiv
Published
2023-05-01
Volume
625
Issue
7994
Pages
352-359
ISSN
0028-0836 (ISSN-L)
DOI
10.1101/2023.05.01.538930
OpenAlex
W4388895886
Cited by
144
References
1
Citations by year
2026: 47 · 2025: 48 · 2024: 37 · 2023: 12
FWCI
23.29
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Nature (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Cancer Research Institute
  • G. Harold and Leila Y. Mathers Foundation (P30 GM124165)
  • Deutsche Forschungsgemeinschaft (464312965, SPP2330)
  • Weizmann Institute of Science
  • Israel Science Foundation
  • Council for Higher Education
  • Division of Chemistry
Topics
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
bacterial immunity, phage resistance, GAD1, GAD-2, TIR domain proteins, immune signaling, phage-host interactions
MeSH terms
Bacteria, Bacterial Proteins, Bacteriophages, DNA, Viral, Viral Proteins, Bacillus Phages, CRISPR-Cas Systems

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