Dual transcriptional profiles during F. nucleatum strain JD-Fn1 infected by a novel bacteriophage JD-Fnp4

Fusobacterium nucleatum is a Gram-negative obligate anaerobic bacteria. Extensive research has confirmed that Fusobacterium nucleatum is strongly associated with several diseases and may have carcinogenic properties. Intervention strategies targeting Fusobacterium nucleatum have become a research focus for the prevention and treatment of related diseases, among which phage therapy, with its ability of specific and targeted modulation of host bacteria, has gained attention increasingly. To guarantee the efficacy and security of phage interventions, it is essential to thoroughly investigate the interaction process between potential phages and their host bacteria. In this study, we conducted the first exploration of the interaction between Fusobacterium nucleatum JD-Fn1 and phage JD-Fnp4 with a wide host spectrum. More than 50% of the host genes displayed differential expression during JD-Fnp4 infection, with CRISPR-related endonuclease genes, type II toxin-antitoxin system toxin genes, and restriction endonuclease subunit genes generally upregulated as JD-Fn1 actively counteracted the infection with JD-Fnp4. In addition, host genes associated with stress-related virulence factors and antibiotic resistance trending downward, suggesting the potential benefit of phage therapy. Additionally, only a small subset of the phage genes displayed temporal expression when phage JD-Fnp4 infected the host bacteria, but the transcription levels of the majority of expressed genes increased over time. These results provide references for investigating the interaction mechanisms between Fusobacterium nucleatum and phages and could lay a molecular basis for further utilization of phages in intervention therapies against related diseases.