An investigation of the molecular mechanism of invasion of human epithelial cells by Campylobacter jejuni using a novel in vitro model based on altering bacterial DNA topology (360G-Wellcome-207002_Z_17_Z)

Campylobacter jejuni is the leading cause of bacterial gastroenteritis in the world. The organism is endemic in chickens where it appears to act as a commensal and is found in high numbers as part of the mucosal microbiome. In contrast the organism is highly pathogenic in humans where it displays an invasive phenotype which results in severe gastroenteritis and damage to the epithelium. The mechanism by which this important human pathogen invades the human epithelium is relatively poorly understood compared to other invasive pathogens primarily down to the fact that the organism invades at a relatively low frequency in vitro. Some studies have suggested the involvement of host cytoskeleton rearrangement whereas others have contradicted these findings. The Ó Cróinín laboratory have recently published data showing that invasion is induced by relaxation of DNA supercoiling using sub-inhibitory concentrations of novobiocin and that this results in a dramatic increase in invasion. The aim of this project is to use this induction of the invasive phenotype to study the interaction of C. jejuni with human epithelial cells in vitro and in particular to study the involvement of actin, tubulin and other host cell cytoskeleton molecules in this process.