Proteomic and Biochemical Characterisation of F. nucleatum Outer Membrane Vesicle

Abstract

Fusobacterium nucleatum, a gram-negative spindle-shaped anaerobic bacterium, is a component of the human microbiome that primarily inhabits the oral cavity and is associated with many diseases, including sinusitis, tonsillitis, urinary tract infection, and inflammatory bowel disease. Recent research demonstrates an association between the presence of this bacterium and colorectal carcinoma.

This study aimed to investigate the ability of this bacterium and its outer membrane vesicles (OMV) to modulate colonic cell function. Like other gram-negative bacteria, F. nucleatum produce OMV, but little is known about how they interact with host tissue. To investigate the potential role of these structures in the host-pathogen interaction the OMV were purified, proteomically characterised and their interaction with colonic cells investigated. In this regard, the mass spectrometry-based proteomic analysis revealed the presence of several biologically active proteases which appeared to be selectively enriched in the OMV. In addition, many other proteins with documented or likely roles in F. nucleatum-mediated pathogenesis were identified.

OMV impaired the barrier function of model colonic epithelial monolayers, in part by degrading the tight junctional protein (E-cadherin), which supports the hypothesis that these nanostructures likely make a significant contribution to the pathogenesis of gastrointestinal disease in susceptible individuals. However, more studies are required to identify the exact mechanisms of F. nucleatum OMV that associated with colorectal cancer.