Determining how phase variation contributes to host colonisation andextraintestinal spread of Campylobacter jejuni

<p dir="ltr">Campylobacter jejuni is the leading cause of human acute gastroenteritis worldwide. On commercial intensive and free-range chicken farms C. jejuni is endemic and transmitted primarily via the faecal-oral route between chickens. Colonisation typically occurs in the caeca, large intestine, and cloaca, but the bacterium can also translocate across the intestinal epithelium into deeper tissues including the liver and spleen. The mechanisms underlying this extraintestinal spread remain poorly understood. This thesis investigated the role of phase variation (PV) in chicken colonisation and dissemination of C. jejuni by performing genomic analyses on experimental data of two generalist and three chicken-specialist strains. Individual PV gene switching was investigated between inoculum and tissue-site isolates (caeca, ileum, liver, and spleen), and six-gene phasotype analyses were used to compare phasotype distributions across tissue sites. Bottleneck simulation models were also applied to diversity and divergence values to identify potential bottleneck events that had occurred during transmission and colonisation. Limited evidence of selective bottlenecks was available for certain PV loci including those associated with flagellar function in spleen and liver isolates. However, the findings of this work suggest that non-PV genes may play a critical role in tissue-specific colonisation and are likely important targets of selection within the chicken host. Improved understanding of C. jejuni and its contribution to within-(chicken)host colonisation and extraintestinal spread will provide valuable insights for development of strategies to limit human exposure through the food chain; ultimately reducing the economic burden of campylobacteriosis.</p>