Characterizing F.nucleatumcomplement resistance

Abstract

Fusobacterium nucleatum (Fn) is a Gram‐negative, anaerobic, oral bacterium that disseminates from the mouth through the bloodstream where it can cause tissue infections, preterm birth, and adverse outcomes in multiple cancers. However, how Fn survives the barrage of immune system attacks while in the bloodstream is wholly unknown. We hypothesized that Fn must be resistant to clearance by the human complement system; a complex network of serum proteins that act to label bacteria and viruses for clearance by immune cells, or directly kill Gram‐negative bacteria by depositing large protein complexes that result in membrane pores and cell death. To test this hypothesis, we incubated Fn with pooled human sera (PHS) with active complement components to determine resistance levels for multiple bacterial strains that are clinically relevant in disease. Here we present varying complement resistance levels in highly similar Fn strains and outline our prediction for the bacterial genes that are driving this immune resistance. These studies have the potential to uncover Fn outer membrane proteins that inactivate the complement system to facilitate their survival and passage throughout the human body. Our goal is to therapeutically target these Fn proteins by disrupting their immune interactions using host‐generated antibodies (vaccine), thereby allowing both the innate and adaptive immune branches to clear these bacteria before they can establish infection and disease.