@article{6f454613e3694242b19cb0747ecb2f54,
title = "Discovery of phage determinants that confer sensitivity to bacterial immune systems",
abstract = "Over the past few years, numerous anti-phage defense systems have been discovered in bacteria. Although 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 177 phage mutants that escape 15 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.",
author = "Avigail Stokar-Avihail and Taya Fedorenko and Jens H{\"o}r and Jeremy Garb and Azita Leavitt and Adi Millman and Gabriela Shulman and Nicole Wojtania and Sarah Melamed and Gil Amitai and Rotem Sorek",
note = "We thank the Sorek lab and A. Bernheim for fruitful discussion and comments. J.H. was funded by the Deutsche Forschungsgemeinschaft (grant 466645764). A.M. was supported by an Ariane de Rothschild Women Doctoral Program fellowship and, in part, by the Israeli Council for Higher Education via the Weizmann Data Science Research Center. R.S. was supported, in part, by the European Research Council (grant ERC-AdG GA 101018520), Israel Science Foundation (personal grant ISF 296/21 and MAPATS grant 2720/22), the Deutsche Forschungsgemeinschaft (SPP 2330, grant 464312965), the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, the Minerva Foundation with funding from the Federal German Ministry for Education and Research, and the Knell Family Center for Microbiology. Author contributions - A.S.-A. and R.S. designed the study. R.S. supervised the study. A.S.-A. performed all experiments and analyses unless otherwise indicated. A.S.-A., T.F., G.S., and N.W. isolated phages. A.S.-A. performed sequencing and computational analyses. J.H. performed northern blots. J.G. and A.S.-A. performed restriction analysis. A.M. computationally detected defense systems. A.L. and A.S.-A. performed toxicity experiments. A.L. and S.M. constructed defense strains. G.A. and A.S.-A. analyzed protein structures. The manuscript was written by A.S.-A. and R.S. All authors contributed to manuscript editing and support the conclusions.",
year = "2023",
month = apr,
day = "27",
doi = "https://doi.org/10.1016/j.cell.2023.02.029",
language = "الإنجليزيّة",
volume = "186",
pages = "1863--1876",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "9",
}