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Discovery of phage determinants that confer sensitivity to bacterial immune systems
Open accessPreprint — published as 10.1016/j.cell.2023.02.029 · Paper page
Abstract
Over the past few years, numerous anti-phage defense systems have been discovered in bacteria. While the mechanism of defense for some of these systems is understood, a major unanswered question is how these systems sense phage infection. To systematically address this question, we isolated 192 phage mutants that escape 19 different defense systems. In many cases, these escaper phages were mutated in the gene sensed by the defense system, enabling us to map the phage determinants that confer sensitivity to bacterial immunity. Our data identify specificity determinants of diverse retron systems and reveal phage-encoded triggers for multiple abortive infection systems. We find general themes in phage sensing and demonstrate that mechanistically diverse systems have converged to sense either the core replication machinery of the phage, phage structural components, or host takeover mechanisms. Combining our data with previous findings, we formulate key principles on how bacterial immune systems sense phage invaders.
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Highly accurate protein structure prediction with AlphaFold
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Metadata
- Authors
- Stokar-Avihail, A., Fedorenko, T., Garb, J., Leavitt, A., Millman, A., Shulman, G., Wojtania, N., Melamed, S., Amitai, G., & Sorek, R.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Sorek, Rotem
- ORCID
- Venue
- Cell
- Publisher
- openRxiv
- Published
- 2022-08-28
- Volume
- 186
- Issue
- 9
- Pages
- 1863-1876.e16
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W4362697030
- Cited by
- 195
- References
- 1
- Citations by year
- 2026: 51 · 2025: 50 · 2024: 67 · 2023: 25 · 2022: 2
- FWCI
- 31.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Minerva Foundation
- Deutsche Forschungsgemeinschaft (464312965, SPP2330)
- Israel Science Foundation (ISF 296/21, SPP 2330)
- Council for Higher Education
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- anti-phage defense systems, bacterial immunity
- MeSH terms
- Bacteria, Bacteriophages, Mutation, Viral Proteins, Bacterial Physiological Phenomena, CRISPR-Cas Systems
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