Elucidating potential virulence factors in Fusobacterium nucleatum
Fusobacterium nucleatum (Fn) is a strictly anaerobic, Gram negative bacterial species that has been implicated in multiple clinical pathologies including periodontal disease, inflammatory bowel disease and colorectal cancer (CRC). The species is unusual in its phenotypic and genotypic heterogeneity, with some strains demonstrating a more virulent phenotype than others; however, the genetic basis for these differences and the association of any particular subspecies of Fn with disease has not yet been proven. With the recent confirmation of the Fusobacterium sequence enrichment in colorectal carcinomas, the characterization of cultured Fn isolates from CRC biopsies was warranted. Fn strains were isolated from human intestinal mucosal biopsies and were phenotypically and genetically analyzed. The invasive, inflammatory potential of Fn in vitro was also assessed. There was extensive variability between the phenotypic, invasive and inflammatory potentials of 8 different CRC-derived Fn strains. Further genetic characterization showed the prevalence of a class of genes of unknown function containing MORN2-domains that were expanded in Fusobacterium spp. known to be highly invasive. Proteins containing MORN2-domains are predicted to be surface-associated and as such may play a role in enabling host cell adherence and invasion by fusobacterial species. In addition, the presence of bacteriophages in Fn strains were also predicted to explain the genomic heterogeneity between Fn strains especially in relation to adherence and invasion. These predictions prompted the exploration of the Fn transcriptome for the purpose of determining the proteins that govern adherence and subsequent invasion of the bacteria into host cells. Going forward, RNA-seq will be used as a tool to help unravel the mechanisms of Fusobacterium pathogenesis. Continuing research in this area will enable the development of diagnostic and therapeutic strategies for the detection and treatment of Fusobacterium-associated diseases.