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TitlePhage parasites targeting phage homologous recombinases provide antiviral immunity.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 1889, Year 2025
Publish dateFeb 22, 2025
AuthorsGianluca Debiasi-Anders / Cuncun Qiao / Amrita Salim / Na Li / Ignacio Mir-Sanchis /
PubMed AbstractBacteria often carry multiple genes encoding anti-phage defense systems, clustered in defense islands and phage satellites. Various unrelated anti-phage defense systems target phage-encoded ...Bacteria often carry multiple genes encoding anti-phage defense systems, clustered in defense islands and phage satellites. Various unrelated anti-phage defense systems target phage-encoded homologous recombinases (HRs) through unclear mechanisms. Here, we show that the phage satellite SaPI2, which does not encode orthodox anti-phage defense systems, provides antiviral immunity mediated by Stl2, the SaPI2-encoded transcriptional repressor. Stl2 targets and inhibits phage-encoded HRs, including Sak and Sak4, two HRs from the Rad52-like and Rad51-like superfamilies. Remarkably, apo Stl2 forms a collar of dimers oligomerizing as closed rings and as filaments, mimicking the quaternary structure of its targets. Stl2 decorates both Sak rings and Sak4 filaments. The oligomerization of Stl2 as a collar of dimers is necessary for its inhibitory activity both in vitro and in vivo. Our results shed light on the mechanisms underlying antiviral immunity against phages carrying divergent HRs.
External linksNat Commun / PubMed:39987160 / PubMed Central
MethodsEM (single particle)
Resolution3.21 - 3.9 Å
Structure data

17821

8pq8

EMDB-17821, PDB-8pq8:
Sak Single Strand Annealing Protein from Staphylococcal Bacteriophage 80a - dCTD
Method: EM (single particle) / Resolution: 3.21 Å

18248

8q86

EMDB-18248, PDB-8q86:
Trimer of the dimeric SaPI2 Stl transcriptional regulator
Method: EM (single particle) / Resolution: 3.69 Å

18346

8qe9

EMDB-18346, PDB-8qe9:
Complex between the 80a-Sak SSAP and the SaPI2 Stl master regulator
Method: EM (single particle) / Resolution: 3.9 Å

19048

8rc5

EMDB-19048, PDB-8rc5:
Complex between the RecA-like Sak4 SSAP and the SaPI2 Stl master regulator
Method: EM (single particle) / Resolution: 3.35 Å

Chemicals

ChemComp-HOH:
WATER

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

Source
  • staphylococcus phage 80alpha (virus)
  • staphylococcus aureus (bacteria)
  • staphylococcus phage 52a (virus)
KeywordsRECOMBINATION / Annealase / SSAP / Single Strand Annealing / Single Strand Binding / Recombineering / SaPI / Bacteriophage / Staphylococcal / Complex / SaPI induction / SaPI2 / Mobile Genetic Element / MGE / PICI / Phage-Inducible Chromosomal Island / C18 / Ring / DNA BINDING PROTEIN / Transcriptional regulator / Stl / Staphylococcus aureus Pathogenicity Island / PICIs / transcriptional repressor / transcription regulator / repressor / DNA-binding / GENE REGULATION / Transcription / Transcriptonal regulator

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