Nicotinamide attenuates the virulence of colorectal cancer-associated <i>Fusobacterium nucleatum</i>

<i>Fusobacterium nucleatum</i> contributes to the progression of colorectal cancer (CRC). Nicotinamide (NAM), a safe, cost-effective, and water-soluble form of vitamin B3, has been shown to inhibit the virulence of various microorganisms. However, its effect on <i>F. nucleatum</i> pathogenicity remains unclear. In this study, we evaluated the effects of NAM on the pathogenic traits of <i>F. nucleatum</i>. A quarter of the minimum inhibitory concentration of NAM (~50 mM) was found to simultaneously inhibit bacterial growth, biofilm formation, and the adhesion and invasion of CRC cells. Transcriptomic analysis of <i>F. nucleatum</i> treated at this concentration revealed that 257 genes were upregulated and 316 genes were downregulated. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology functional enrichment analyses indicated that these differentially expressed genes are involved in multiple pathways, including oxidative phosphorylation, biofilm formation, two-component systems, ATP synthesis, and other processes. Furthermore, we showed that NAM, as a class III histone deacetylase inhibitor, could inhibit the deacetylase activity of CobB, thereby increasing the acetylation level of the FomA and reducing its binding ability to CRC cells. In summary, these findings suggest that NAM can attenuate multiple virulence traits of <i>F. nucleatum</i> and may serve as a promising <i>F. nucleatum-</i>targeted strategy for prevention and treatment of CRC.