Surviving the Enterohepatic Tract: Molecular Mechanisms of Stress Adaptation in Helicobacter hepaticus

Chronic inflammation is a precursor for metaplastic and dysplastic changes in diverse organs of the mammalian digestive tract, and can lead to carcinogenesis. Chronic hepatitis is a precursor for hepatocellular carcinoma, and can be caused by an infection with hepatitis B and C virus, alcohol and medicine abuse (3). Approximately ten percent of the patients with chronic hepatitis in a non-cirrhotic liver do not have any of the known risk factors, and it has been suggested that chronic colonization by an unknown Helicobacter species may contribute to disease development in these cases (7). The role of Helicobacter spp. in the development of hepatitis and hepatocellular carcinoma could be similar to that of Helicobacter pylori and the development of gastric ulceration and gastric carcinoma. Helicobacter hepaticus colonizes the intestinal and hepatobiliary tract of rodents, and is thought to represent an excellent model for the research on yet unknown human enterohepatic Helicobacter species. H. hepaticus colonizes different niches: the intestine, liver and bile ducts. This suggests that the organism is well adapted to the variable and hostile conditions thought to occur there. The ability to survive and grow in these different environments is thought to be established through the capability to cope with toxic environmental factors derived from both medication and the host immune system. The research presented in this thesis was aimed to investigate the molecular mechanisms underlying stress adaptation mechanisms of H. hepaticus. This should give us a better insight in the development of the diseases related to H. hepaticus, and the role that such mechanisms play in the evolutionary differentiation of Helicobacter species as shown by their ability to colonize different niches.

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