Mining a vibriophage depolymerase for enhanced pathogen control in aquaculture

Area of Science:

• Microbiology
• Biotechnology
• Aquaculture Science

Background:

• Antibiotic resistance in *Vibrio* species poses a significant threat to global aquaculture.
• Bacteriophages (phages) and their derived enzymes, particularly depolymerases, show promise as alternatives to antibiotics.
• Phage depolymerases can degrade bacterial surface polysaccharides, potentially enhancing antibacterial efficacy and overcoming resistance.

Purpose of the Study:

• To identify and characterize novel phage-encoded depolymerases targeting *Vibrio* pathogens.
• To evaluate the antibiofilm activity and synergistic potential of a novel depolymerase (Dep193) in combination with a phage (VnaP).
• To explore the therapeutic potential of phage depolymerases for controlling *Vibrio* infections in aquaculture.

Main Methods:

• Bioinformatic analysis of *Vibrio* phages to identify putative depolymerase genes.
• Isolation and characterization of a depolymerase-encoding phage (VnaP) and its associated depolymerase (Dep193).
• Genome sequencing, heterologous expression, enzymatic activity assays, antibiofilm assays, and synergistic efficacy studies.

Main Results:

• A high prevalence of putative depolymerase genes was found in *Vibrio* phages.
• A novel polysaccharide depolymerase, Dep193, was identified and characterized, showing efficient degradation of *Vibrio* surface polysaccharides and potent antibiofilm activity.
• The combination of Dep193 and phage VnaP demonstrated synergistic activity, significantly enhancing bacterial clearance and delaying resistance emergence in multiple *Vibrio* species.

Conclusions:

• Dep193 is the first biochemically validated *Vibrio* phage depolymerase, expanding the known diversity of these enzymes.
• The Dep193-VnaP combination represents a potent and synergistic therapeutic strategy for controlling *Vibrio* infections in aquaculture.
• This study highlights the potential of phage-derived depolymerases as effective alternatives to antibiotics in combating resistant bacterial pathogens.