Phage Φ170 biocontrol of multidrug-resistant Vibrio parahaemolyticus in a zebrafish model

Vibrio parahaemolyticus is an important zoonotic pathogen that poses a persistent threat to aquaculture systems and food safety. The rapid emergence of multidrug resistance, driven by increasing antibiotic selection pressure, highlights the urgent need for alternative antimicrobial strategies, among which phage therapy has emerged as a promising candidate. Here, we reported the isolation of a bacteriophage, designated Φ170, targeting multidrug-resistant Vibrio parahaemolyticus from sewage collected at a shrimp farm. Φ170 exhibited a latent period of 10 min, an eclipse period of approximately 60 min, and an average burst size of 426 PFU per cell. The phage also showed broad tolerance to pH and temperature. Φ170 displayed rapid and potent lytic activity, effectively suppressing host bacterial growth within 6 h post-infection. To further assess its in vivo efficacy, we evaluated the prophylactic and therapeutic potential of phage administration by immersion in zebrafish challenged with Vibrio parahaemolyticus. Prophylactic treatment with Φ170 significantly increased zebrafish survival within 72 h. Moreover, combined treatment with Φ170 and doxycycline exerted a synergistic effect, effectively reducing bacterial loads, alleviating liver and intestine tissue damage, and suppressing excessive inflammatory responses. Collectively, these findings indicated that phage Φ170 represented a promising prophylactic agent against Vibrio parahaemolyticus infection and that combined phage therapy with antibiotics provided an effective strategy for treating drug-resistant Vibrio parahaemolyticus infections.IMPORTANCEPhage therapy is a promising strategy for combating bacterial infections, serving as a complementary therapy to antibiotics and a synergistic approach in combination treatments with antimicrobial agents. To address infections by multidrug-resistant (MDR) Vibrio parahaemolyticus, we isolated and characterized bacteriophage Φ170, which is capable of lysing MDR Vibrio parahaemolyticus. We evaluated its prophylactic and therapeutic potential in a zebrafish infection model. We found that phage Φ170 exhibited strong lytic activity both in vitro and in vivo, effectively preventing Vibrio parahaemolyticus infection and displaying synergistic antibacterial effects when combined with antibiotics. Phage-antibiotic combination therapy further enhanced therapeutic efficacy in infected zebrafish. Our results provide experimental support for phage-antibiotic combination strategies against MDR bacterial infections and highlight the potential of phage therapy for the prevention and treatment of Vibrio parahaemolyticus infections.