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.

• Authors: Nitzan Tal, Adi Millman, Avigail Stokar-Avihail, Taya Fedorenko, Azita Leavitt, Sarah Melamed, Erez Yirmiya, Carmel Avraham, Alexander Brandis, Tevie Mehlman, Gil Amitai, Rotem Sorek
• Journal: Nature microbiology (Nat Microbiol) Vol. 7 Issue 8 Pg. 1200-1209 (08 2022) ISSN: 2058-5276 [Electronic] England
• PMID: 35817891 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Antiviral Agents
• SAM Domain and HD Domain-Containing Protein 1
• Deoxyguanosine

Topics

• Antiviral Agents
• Bacteria
• Bacteriophages (genetics)
• Deoxyguanosine
• Humans
• SAM Domain and HD Domain-Containing Protein 1