Characterization of Fusobacterium varium Fv113-g1 isolated from a patient with ulcerative colitis based on complete genome sequence and transcriptome analysis

Abstract

Fusobacterium spp. present in the oral and gut flora is carcinogenic and is associated with the risk of pancreatic and colorectal cancers. Fusobacterium spp. is also implicated in a broad spectrum of human pathologies, including Crohn’s disease and ulcerative colitis (UC). Here we report the complete genome sequence of Fusobacterium varium Fv113-g1 (genome size, 3.96 Mb) isolated from a patient with UC. Comparative genome analyses totally suggested that Fv113-g1 is basically assigned as F. varium, in particular, it could be reclassified as notable F. varium subsp. similar to F. ulcerans because of partial shared orthologs. Compared with the genome sequences of F. varium ATCC 27725 (genome size, 3.30 Mb) and other strains of Fusobacterium spp., Fv113-g1 possesses many accessary pan-genome sequences with noteworthy multiple virulence factors, including 44 autotransporters (type V secretion system, T5SS) and 13 Fusobacterium adhesion (FadA) paralogs involved in potential mucosal inflammation. Indeed, transcriptome analysis demonstrated that Fv113-g1-specific accessary genes, such as multiple T5SS and fadA paralogs, showed notably increased expression with D-MEM cultivation than with brain heart infusion broth. This implied that growth condition may enhance the expression of such potential virulence factors, leading to remarkable survival against other gut microorganisms and to the pathogenicity to human intestinal epithelium.

Metagenomic analyses of the gut microbiota associated with colorectal adenoma

“…nucleatum , F . varium [9] has also recently gained notoriety as a gastrointestinal pathogen [10, 11]. Indeed, links between the enrichment of Fusobacterium spp.…”

Southern Chinese populations harbour non-nucleatum Fusobacteria possessing homologues of the colorectal cancer-associated FadA virulence factor

“…Gut microbiota surveys in Japanese cohorts have indicated that F. varium is associated with UC, 21 22 and a genome sequencing study of F. varium strain Fv113-g1 isolated from a UC patient reported expression of FadA homologues in monocultures simulating in vivo conditions within the human gut. 68 Our data on FadA homologues show that sequences from the Fusobacterium _A clade ( F. varium , F. ulcerans and other uncharacterised sister taxa) are not identical to sequences from the Fusobacterium clade (in which the CRC-associated F. nucleatum is located) ( figure 4 ), thereby suggesting distinct functions or targets among these homologues. While the presence/absence of these gene homologues do not directly translate to invasiveness, 69 we postulate that Fusobacterium _A taxa and their copies of the FadA homologue can be risk factors for diseases other than CRC.…”

“…As for F. varium and F. ulcerans , less is known about their distribution and association with cancers or disease. Gut microbiota surveys in Japanese cohorts have indicated that F. varium is associated with UC,21 22 and a genome sequencing study of F. varium strain Fv113-g1 isolated from a UC patient reported expression of FadA homologues in monocultures simulating in vivo conditions within the human gut 68. Our data on FadA homologues show that sequences from the Fusobacterium _A clade ( F. varium , F. ulcerans and other uncharacterised sister taxa) are not identical to sequences from the Fusobacterium clade (in which the CRC-associated F. nucleatum is located) (figure 4), thereby suggesting distinct functions or targets among these homologues.…”

Mucosal microbiota and gene expression are associated with long-term remission after discontinuation of adalimumab in ulcerative colitis

“…(one OTU) and Veillonella dispar (one OTU). Specific species of Fusobacterium, such as F. nucleatum and F. varium, were reported to be associated with the promotion of intestinal inflammation 18,19 . The population of V. dispar was shown to be significantly larger in patients with severe disease compared to those with mild disease in a large-scale study of gut bacterial communities affected by IBD 20 .…”