biostudies-literatureYue YShandong Provincial Postdoctoral Science FoundationTaishan Industrial Experts ProgrammeNational Natural Science Foundation of ChinaQingdao Postdoctoral Science FoundationPostdoctoral Fellowship Program of CPSFe0182425https://www.ebi.ac.uk/biostudies/studies/S-EPMC12915355biostudies-literatureUnknown92(2)Despite the promise of phages as antibiotic alternatives, their efficacy is often undermined by the rapid emergence of bacterial resistance. Phage-derived enzymes, particularly depolymerases, offer a compelling strategy to overcome this limitation and enhance antibacterial therapy. Focusing on <i>Vibrio</i> pathogens, the major threats to global aquaculture, our bioinformatic analysis revealed that 79.4% of cultured and 46.2% of uncultured <i>Vibrio</i> phages encode putative depolymerases, underscoring a vast but underexploited antibacterial resource. We further isolated and characterized VnaP, a depolymerase-encoding phage (novel genus, <i>Caudovircetes</i>) that forms distinctive halo plaques indicative of depolymerase activity. Genome analysis identified ORF193, encoding a novel polysaApplied and environmental microbiologyMining a vibriophage depolymerase for enhanced pathogen control in aquaculture.PMC1291535542476115SDCX-ZG-20240018642576102GZC20232809QDBSH20240102185tscy20241164220612442406120He YLi CZhang YYin RZhao JWang ZYue YfalseMining a vibriophage depolymerase for enhanced pathogen control in aquaculture.Despite the promise of phages as antibiotic alternatives, their efficacy is often undermined by the rapid emergence of bacterial resistance. Phage-derived enzymes, particularly depolymerases, offer a compelling strategy to overcome this limitation and enhance antibacterial therapy. Focusing on <i>Vibrio</i> pathogens, the major threats to global aquaculture, our bioinformatic analysis revealed that 79.4% of cultured and 46.2% of uncultured <i>Vibrio</i> phages encode putative depolymerases, underscoring a vast but underexploited antibacterial resource. We further isolated and characterized VnaP, a depolymerase-encoding phage (novel genus, <i>Caudovircetes</i>) that forms distinctive halo plaques indicative of depolymerase activity. Genome analysis identified ORF193, encoding a novel polysa2026-01-01T00:00:00Z2026 Feb2026-07-16T06:38:40.269Z2026-07-09T10:39:56.188ZS-EPMC129153554152441710.1128/aem.01824-25