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Mode of Action (MoA)
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binds to the OLD exonuclease.
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Evidence
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Oad1 (OLD-antidefense 1) was identified as a direct anti-defense factor encoded by the ICP1 phage, capable of inhibiting the activity of the Class 1 OLD family nuclease Vc OLD. Comparative infection assays showed that ICP1⁽²⁰¹⁸⁾, unlike other ICP1 isolates, was able to robustly infect V. cholerae expressing Vc OLD, indicating the presence of a counter-defense mechanism. Plasmid-based expression (ECO_0000017) of candidate genes from ICP1⁽²⁰¹⁸⁾ revealed that only Gp205⁽²⁰¹⁸⁾ (Oad1) enabled ICP1⁽²⁰⁰⁶⁾ to overcome Vc OLD restriction, while the closely related Gp205⁽²⁰⁰⁶⁾ did not. Allelic swaps confirmed that Oad1 was sufficient to restore phage infectivity in a gp205-deletion mutant, and this activity extended to rescuing plaque size of the unrelated ICP3 phage. Mutational analysis pinpointed key residues (S135, K136, N144) in Oad1 important for counter-defense. Finally, co-immunoprecipitation (ECO_0000085) assays demonstrated a specific in vivo physical interaction between Oad1 and Vc OLD, absent with the non-functional Gp205⁽²⁰⁰⁶⁾ allele, confirming direct inhibition of Vc OLD by Oad1.
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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 Class 1 OLD nucleases
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Relevant publication(s)
DOI
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10.1101/2025.01.06.631583
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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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Old exonuclease
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