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Mode of Action (MoA)
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binds the toxin, DarT.
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Evidence
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AdfB (anti-DarT factor B) was identified as a phage-encoded anti-defense factor through selection and sequencing of ICP1 phage mutants that escaped restriction by the DarTG toxin-antitoxin system in clinical V. cholerae isolates. A conserved G62D mutation in the ICP1 core genome gene gp145 conferred escape from DarTG-mediated restriction. Deletion of gp145 abolished this escape (ECO_0007379), while complementation with the G62D allele restored it, confirming functional necessity. Genome replication assays revealed that only phage encoding Gp145D62 (AdfB) restored ICP1 DNA replication in the presence of DarTG, directly linking AdfB function to anti-DarT activity. Inducible expression of Gp145D62 in V. cholerae abrogated DarT-mediated cell death, similar to the native antitoxin DarG, while wild-type Gp145G62 did not. Bacterial two-hybrid assays showed that Gp145D62, but not Gp145G62, physically interacted with DarT, and this interaction was disrupted by a Y82A mutation in DarT’s DNA-binding domain. Structural modeling suggested that Gp145D62 mimics the C-terminal DNA-binding inhibitory domain of DarG. Collectively, these data demonstrate that Gp145D62 (AdfB) directly binds and neutralizes DarT toxin activity, allowing phage escape from host defense.
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MoA Category
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binds and inhibits host defence system
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Subtype(s) of the defence system(s) inhibited by the protein
Defence Subtype
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Vibrio cholerae type IV TA system DarTG
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Relevant publication(s)
DOI
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10.1128/mbio.00111-24
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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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-
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Genome(s) encoding the protein
Protein Source
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Vibrio phage ICP1
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Defence system(s) inhibited by the protein
Defences
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TA
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