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Mode of Action (MoA)
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binds the signalling molecule (1′′–3′ gcADPR)
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Evidence
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Gene was identified based on differential sensitivity to the Thoeris defence systems — among closely related phages infecting Bacillus subtilis, all phages were sensitive to the Thoeris defence systems, apart from SBSphiJ7. Ectopic expression (ECO_0000017) of Tad1 into B. subtilis cells that also express the Thoeris system from Bacillus cereus MSX-D12 rendered phages usually sensitive to Thoeris resistant to the defence system. Silencing of tad1 in the phage SBSphiJ7 using dCas9 restored Thoeris defense, proving that Tad1 is necessary for immune evasion. To detect signalling molecules, lysates from Thoeris-expressing cells infected with phage lacking Tad1 and triggered ThsA NADase activity, but co-expression with Tad1 abolished this activity, indicating that Tad1 interferes upstream of ThsA activation. Adding purified Tad1 to signalling-containing lysates eliminated the ThsA activation signal, indicating Tad1 directly binds and sequesters the signalling molecule. Tad1 was crystallised (ECO_0001823) in complex with the signalling molecule (1′′–2′ gcADPR).
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MoA Category
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degrades or sequesters molecules utilised by host defence systems
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Subtype(s) of the defence system(s) inhibited by the protein
Defence Subtype
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Bacillus subtilis BEST7003 type I Thoeris;Pseudomonas aeruginosa type II-A and type III-C CBASS
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Relevant publication(s)
DOI
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10.1038/s41586-022-05375-9
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Other components of the anti-defence system
Multicomponent System
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-
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Known structure in PDB
PDB ID
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7UAV_A
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Genome(s) encoding the protein
Protein Source
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Bacillus phage SBSphiJ7
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Defence system(s) inhibited by the protein
Defences
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Thoeris,
CBASS
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