Front Microbiol. 2026 Jun 1;17:1816537. doi: 10.3389/fmicb.2026.1816537. eCollection 2026.
ABSTRACT
American foulbrood (AFB), caused by the spore-forming bacterium Paenibacillus larvae, is the most destructive bacterial brood disease of Apis mellifera. Control is challenging because endospores persist for decades and antibiotic use is restricted by regulations, resistance, and residue concerns. Bacteriophages have re-emerged as a species-specific, residue-free strategy for AFB prevention and treatment. A PRISMA-guided systematic review was conducted searching PubMed, Embase, and Web of Science using the terms (bacteriophage OR phage) AND (honeybee OR Apis mellifera). A total of 90 records were retrieved; after deduplication (19 removed), 71 titles and abstracts were screened. Eleven full texts were assessed for eligibility. Nine studies met inclusion criteria: three in adult bees or colonies, four in larvae, and two in vitro. Across studies, 27 P. larvae phages were characterized in vitro, 18 tested in larval assays, and nine evaluated at the hive level, mainly via oral delivery. In a controlled hive trial, a three-phage cocktail provided complete protection from natural AFB (100% protected vs. 80% infection in controls; p < 0.05) and enabled full recovery within 2 weeks, performing comparably to or better than prophylactic antibiotics. Larval studies generally showed significantly improved survival with prophylactic or therapeutic dosing, though efficacy varied by phage. A biodistribution study found limited indirect larval exposure after adult feeding (~32 PFU/larva at 24 h), indicating hive-mediated inactivation as a key translational barrier. One phage bound both vegetative cells and spores while retaining ~93% in-vitro infectivity. Overall, phage cocktails show strong proof-of-concept, with formulation, delivery, and rational cocktail design as key translational priorities.
PMID:42305668 | PMC:PMC13265389 | DOI:10.3389/fmicb.2026.1816537