thesis
Surviving the Enterohepatic Tract: Molecular Mechanisms of Stress Adaptation in Helicobacter hepaticus
- Publication date
- 14 November 2007
- Publisher
- 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.