Fusolisin, the Fusobacterium Protease that Paralyzes Natural Killer Cells

Fusobacterium nucleatum (FN) is a bacterium commonly found in the human oral cavity. It is associated with numerous diseases, including adverse pregnancy outcomes, and colorectal cancer. One crucial protease for FN prosperity is Fusolisn. Fusolisin is essential for acquisition of nutrients and capable of degrading IgA. Fusobacteria are slowly grown and require anaerobic conditions. Hence, to study Fusolisin`s impact on the immune component, we expressed and purified it in Escherichia coli (E. coli), performing codon-optimization to increase the translational efficiency.
Natural killer (NK) cells are innate immune cells capable of eliminating hazardous cells as well as directly killing pathogens. Not only can NK cells directly kill bacteria, but they also impact other immune arms in response to bacterial infections via cytokine secretion. Interestingly, we witnessed a decrease in the surface levels of specific NK cell activating receptors following treatment with Fusolisin. Notably, the expression of CD16, an Fc receptor for IgG mediating antibody-dependent cellular cytotoxicity (ADCC), was dramatically reduced to background levels. Indeed, following Fusolisin treatment, NK cell degranulation and killing were reduced to base line levels both with and without the presence of ADCC mediating antibodies.
We next plan to examine the efficiency of Fusolisin treatment of NK cells in tumor regulation in in-vivo models and to identify the cleavage site(s) of the relevant receptors.
This study may have therapeutic implications for FN associated diseases, as inhibition of Fusolisin may cripple not only the prosperity of FN, but also the paralysis of NK cells.