Bacteria deplete deoxynucleotides to defend against bacteriophage infection.
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
16
12
2021
accepted:
23
05
2022
pubmed:
12
7
2022
medline:
9
8
2022
entrez:
11
7
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35817891
doi: 10.1038/s41564-022-01158-0
pii: 10.1038/s41564-022-01158-0
doi:
Substances chimiques
Antiviral Agents
0
SAM Domain and HD Domain-Containing Protein 1
EC 3.1.5.-
Deoxyguanosine
G9481N71RO
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1200-1209Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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