Campylobacter jejuni Capsular Heptose: Moderation of Host Macrophages and Substrate Channeling During Synthesis
Abstract
With the majority of Canadian Campylobacter jejuni infections resulting from contaminated poultry, I investigated how the strain NCTC 11168 capsular heptose modulates host macrophage activation, and bacterial clearance. Activation was assessed by ELISAs, Griess assays, qRT-PCR, and cytokine multiplex, while looking at adhesion to, uptake by, and survival within host macrophages. The heptose was immunosuppressive in chicken, but not human, macrophages and did not significantly impact clearance by tested host macrophages. It is also likely that heptose biosynthesis enzymes engage in substrate channelling, as previous data indicates that these enzymes have a means to limit degradation of unstable intermediates within the bacterial cytosol. Interactions between heptose biosynthesis enzymes were assessed by surface plasmon resonance, which indicates that enzymes in the heptose modification pathways can bind. This work determines how the capsular heptose alters the activity of host macrophages, while investigating if enzymatic interactions can be exploited to modulate heptose production.