Zebrafish as an effective model for evaluating phage therapy in bacterial infections: a promising strategy against human pathogens

ABSTRACT The escalating prevalence of antibiotic-resistant bacterial infections necessitates urgent alternative therapeutic strategies. Phage therapy, which employs bacteriophages to specifically target pathogenic bacteria, emerges as a promising solution. This review examines the efficacy of phage therapy in zebrafish models, both embryos and adults, which are proven and reliable for simulating human infectious diseases. We synthesize findings from recent studies that utilized these models to assess phage treatments against various bacterial pathogens, including Enterococcus faecalis , Pseudomonas aeruginosa , Mycobacterium abscessus , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , and Escherichia coli . Methods of phage administration, such as circulation injection and bath immersion, are detailed alongside evaluations of survival rates and bacterial load reductions. Notably, combination therapies of phages with antibiotics show enhanced efficacy, as evidenced by improved survival rates and synergistic effects in reducing bacterial loads. We also discuss the transition from zebrafish embryos to adult models, emphasizing the increased complexity of immune responses. This review highlights the valuable contribution of the zebrafish model to advancing phage therapy research, particularly in the face of rising antibiotic resistance and the urgent need for alternative treatments.