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Abstract
Enterohepatic Helicobacter species (EHS) are emerging infectious disease agents. Infection of the enterohepatobiliary tract of several mammals by this group of bacteria results in various pathological disorders. The availability of the Helicobacter hepaticus sequenced and annotated genome, allowed molecular characterisation of the responses of H. hepaticus to host factors such as bile. The adaptation/responses of the bacterium to bovine, porcine and human bile were investigated using proteomics and transcriptomics. Ninety-one different proteins were identified in the responses of H. hepaticus response to the three types of bile. These proteins participate in several key cellular processes including DNA replication; protein transcription, translation and folding; oxidative stress response; motility; virulence; and metabolism. In particular, the bacteria deployed several strategies such as inhibition of the TCA cycle and the electron transport chain as well as iron sequestration to ensure control of the levels of hydroxyl radicals. The results of this study revealed also the modulation by bile of the expression of H. hepaticus genes involved in response to oxidative stress and virulence. The responses of human HEp-2 and Huh7-derived cell-lines to H. hepaticus and Helicobacter bilis, respectively, were investigated employing proteomics and transcriptomics. One-hundred and twenty different proteins were differentially expressed in the responses of the human cells to the presence of Helicobacter spp. in the cell cultures. These proteins are involved in regulation of cell proliferation and structure; metabolism; protein transcription, translation and modification; stress response; and tumour induction. For example, in co-cultures of Huh7-derived cells and H. bilis, the activation of several mitochondrial and endoplasmic reticulum stress-related proteins and the dysregulation of several apoptosis effectors were suggested as mechanisms that could result in the death of the liver cells. Importantly, the differential expression of several tumour-related proteins by the Huh7 cells supported a possible role for Helicobacter spp. in liver cancer.