Characterisation of Novel Fusobacterium Nucleatum Bacteriophages and Their Efficacy in Disrupting Pathogenic Dual-Species Biofilms.

Background:The targeted manipulation of the microbiome using bacteriophages represents a novel approach for addressing antibiotic resistance and polymicrobial diseases. Objective:To isolate and characterise bacteriophages for key bacteria associated with pathogenic periodontal biofilms. Design:Using standard microbiological and bioinformatics techniques, this study isolated and characterized lytic (FNU2 and FNU3) and temperate (FNU4) bacteriophages specific to Fusobacterium nucleatum, a key bacterium in oral biofilms linked to periodontitis and a range of cancers. Results:Morphological and genomic analyses revealed distinct features, with FNU2 and FNU3 classified as Latrobevirus and FNU4 as an unclassified Caudoviricetes. Comparative bioinformatic analysis revealed various defence and anti-defence systems in bacterial hosts and bacteriophages, highlighting complex interactions. Functional assays demonstrated the efficacy of these bacteriophages in disrupting single-species F. nucleatum biofilms and dual-species biofilms of F. nucleatum and Porphyromonas gingivalis. Conclusion:These findings highlight the potential of F. nucleatum-specific bacteriophages as precise tools for microbiome modulation in chronic diseases such as periodontitis and cancer.