@article{11080d8c8bbe402ba47f2ae9c3f242ed,
title = "Bacteria deplete deoxynucleotides to defend against bacteriophage infection",
abstract = "DNA viruses and retroviruses consume large quantities of deoxynucleotides (dNTPs) when replicating. The human antiviral factor SAMHD1 takes advantage of this vulnerability in the viral lifecycle, and inhibits viral replication by degrading dNTPs into their constituent deoxynucleosides and inorganic phosphate. Here, we report that bacteria use a similar strategy to defend against bacteriophage infection. We identify a family of defensive bacterial deoxycytidine triphosphate (dCTP) deaminase proteins that convert dCTP into deoxyuracil nucleotides in response to phage infection. We also identify a family of phage resistance genes that encode deoxyguanosine triphosphatase (dGTPase) enzymes, which degrade dGTP into phosphate-free deoxyguanosine and are distant homologues of human SAMHD1. Our results suggest that bacterial defensive proteins deplete specific deoxynucleotides (either dCTP or dGTP) from the nucleotide pool during phage infection, thus starving the phage of an essential DNA building block and halting its replication. Our study shows that manipulation of the dNTP pool is a potent antiviral strategy shared by both prokaryotes and eukaryotes.",
author = "Nitzan Tal and Adi Millman and \{Stokar Avihail\}, Avigail and Taya Fedorenko and Azita Leavitt and Sarah Melamed and Erez Yirmiya and Carmel Avraham and Alexander Brandis and Tevie Mehlman and Gil Amitai and Rotem Sorek",
note = "Funding Information: We would like to thank P. Cossart for directing us to the SAMHD1 antiviral mechanism, and A. Bernheim and the Sorek laboratory members for comments on earlier versions of this manuscript and fruitful discussion. R.S. was supported, in part, by the European Research Council (grant no. ERC-CoG 681203), Israel Science Foundation (grant no. ISF 296/21), the Deutsche Forschungsgemeinschaft (SPP 2330, grant no. 464312965), the Ernest and Bonnie Beutler Research Programme of Excellence in Genomic Medicine, the Minerva Foundation with funding from the Federal German Ministry for Education and Research, the Knell Family Centre for Microbiology, the Yotam project and the Weizmann Institute Sustainability And Energy Research (SAERI) initiative, and the Dr Barry Sherman Institute for Medicinal Chemistry. A.M. was supported by a fellowship from the Ariane de Rothschild Women Doctoral Programme and, in part, by the Israeli Council for Higher Education via the Weizmann Data Science Research Centre, and by a research grant from Madame Olga Klein-Astrachan. Protein MS was performed at the Weizmann De Botton Protein Profiling Institute. Funding Information: We would like to thank P. Cossart for directing us to the SAMHD1 antiviral mechanism, and A. Bernheim and the Sorek laboratory members for comments on earlier versions of this manuscript and fruitful discussion. R.S. was supported, in part, by the European Research Council (grant no. ERC-CoG 681203), Israel Science Foundation (grant no. ISF 296/21), the Deutsche Forschungsgemeinschaft (SPP 2330, grant no. 464312965), the Ernest and Bonnie Beutler Research Programme of Excellence in Genomic Medicine, the Minerva Foundation with funding from the Federal German Ministry for Education and Research, the Knell Family Centre for Microbiology, the Yotam project and the Weizmann Institute Sustainability And Energy Research (SAERI) initiative, and the Dr Barry Sherman Institute for Medicinal Chemistry. A.M. was supported by a fellowship from the Ariane de Rothschild Women Doctoral Programme and, in part, by the Israeli Council for Higher Education via the Weizmann Data Science Research Centre, and by a research grant from Madame Olga Klein-Astrachan. Protein MS was performed at the Weizmann De Botton Protein Profiling Institute. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2022",
month = aug,
doi = "10.1038/s41564-022-01158-0",
language = "English",
volume = "7",
pages = "1200--1209",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "Nature Research",
number = "8",
}