Determining the virulence determinants of Fusobacterium nucleatum to define diagnostic and therapeutic targets for colorectal cancer

A substantial portion of the cancer burden worldwide is attributable to infectious agents (viruses or bacteria). Some of these can directly cause cancers, others can facilitate cancer development, and the rest may have no causative role but their existence can indicate the presence of a cancer or risk of developing one.

Recently, Fusobacterium nucleatum, a bacterium present on mucosal surfaces, has been found to be highly elevated in a subset of colorectal cancers. F. nucleatum is an invasive bacterium that can cause acute oral and gastrointestinal infections and can act as a pro-inflammatory agent, thus it is a reasonable candidate for having a facilitating role in tumorigenesis. However, F. nucleatum is also well recognized as a benign resident of mucosal surfaces in the absence of pathology. The reason why F. nucleatum may in some cases be pathogenic and at other times an apparently benign, commensal organism is not yet completely understood.

The overall goal of this study is to identify gene(s) associated with F. nucleatum virulence, and to determine how expression levels of these genes are modulated during infection using RNA-Seq. The Canadian Cancer Society estimates that currently 12 percent of all cancer deaths in Canada are attributed to colorectal cancers; a tendency toward late diagnosis indicates a dire need for simple strategies to help detect colorectal cancers early. The finding that F. nucleatum is strongly associated with a significant number of colorectal cancers cases raises the possibility of developing a simple diagnostic pre-screen for the disease, enhancing early detection rates. The proposed work will identify the F. nucleatum genes that are associated with the disease, creating a signature that will markedly increase specificity of new screening tests. Moreover, this study will indicate how pathogenic F. nucleatum strains cause disease, dramatically increasing our knowledge of this enigmatic bacterium and its interactions with host cells that lead to oncogenesis.

Armed with this new knowledge, it will be possible to develop novel diagnostics, and create new tools such as vaccines to combat, and even prevent, infection. Knowledge translation activities for this study will include presenting results at conferences, writing papers and building on the network between the BC Cancer Agency and our anaerobic bacteriology collaborators at the University of Guelph.