Fusobacterium nucleatum - BacteriOncology
A long anaerobic rod, F. nucleatum plays a key role in the development of the oral biofilm. F. nucleatum is unique in its ability to attach to a diverse range of targets. This attachment, bridges between the different members of the dental plaque and contributes to the plaque's structural stability. F. nucleatum is also the oral pathogen most frequently isolated from systemic infections and recently acknowledged for its involvement in adverse pregnancy outcomes and its association with colorectal carcinoma.
Two 2012 back to back articles that analyzed nucleic acid sequences associated with colorectal carcinoma found marked over-representation of F. nucleatum sequences in tumors compared to adjacent control specimens. In our continuous collaboration with Ofer Mandelboim and using unique tools for genetic manipulation in fusobacteria, we showed that tumor-attached fusobateria protect the tumor cells from killing by NK cells and by T cells. This, by activating the immune cells TIGIT suppressor receptor with the fusobacterial Fap2 outer surface protein.
We then continued, and using a mouse colorectal carcinoma model demonstrated that blood-borne fusobacteria (common in transient bacteremia frequent during periodontal disease) are trafficked to the tumors by binding tumor-displayed Gal-GalNAc using the fusobacteria Fap2 protein found to act as a Gal-GalNAc lectin.
Next we found that many tumors display Gal-GalNAc including breast cancer. Based on our knowledge of fusobacterial homing to tumors we are exploring ways to use fusobacteria for detecting and treating cancer.
NK cells are involved in killing viral infected cells and tumor cells. It was therefore surprising when Ofer Mandelboim' group and ours found that a F. nucleatum protein activates the NK cells NKp46 killing activation receptor. This collaboration is ongoing to reveal additional bacteria that interact with NK cells. As NK cells are imperative in combating cancer, we hypothesize that such bacteria can be utilize to treat cancer.
Fusolisin discovered by us. Doron L. PLoS One. 2014.
Gur C., et al, Immunity. 2015
Abed A. et al, Cell Host Microbe. 2016