Using genotype-to-phenotype analyses to identify the genetic determinants of gastroenteritis caused by the food-borne pathogen Campylobacter jejuni.

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Campylobacter jejuni is the major causative agent of foodborne gastroenteritis across Europe. Contaminated chicken meat is the main source of infections and hence control of this pathogen is critical to food security in the poultry industry.The three major virulence determinants of C. jejuni are capsule, lipooligosaccharide and flagella. These structures are important for survival and colonisation of Campylobacter. Consequently, evasion of the immune system is paramount as these structures possess potential immunodominant epitopes that would otherwise result in early recognition of C. jejuni and its subsequent clearance.One mechanism of immune evasion is the decoration of protein structures with a variety of sugar molecules (glycans). A conserved epitope recognised by TLR-5 on the flagellin protein has been lost in C. jejuni. Loss of this epitope renders other bacteria, such as Salmonella, non-motile. However, the structural instability introduced into the flagella through mutations in the TLR-5 epitope has been compensated for by glycosylation of outer domains of the flagellin subunits (Kreutzberger et al., 2020). This highlights the degree to which glycans can play in the survival and immune evasion of Campylobacter. Further, these glycans are highly variable between strains due to differences in gene content, allelic variation and phase variation. Phase variation is a reversible mechanism that leads to ON/OFF switching of gene expression for contingency loci associated with homopolymeric tracts. This leads to different phenotypes through varied expression of genes, whether they are ON/OFF, and what combination is expressed. In our lab, it was shown that a delayed antibody response was observed in birds challenged with glycosylated FlaA when compared to recombinant FlaA protein. Therefore, our research aims to further investigate the contribution of genetic elements that introduce phenotypic variation towards Campylobacteriosis and the survival of Campylobacter.