Effects of human and porcine bile on the proteome of Helicobacter hepaticus

The 2-DE and mass spectrometry analyses of the proteome revealed that 46 proteins of H. hepaticus were differentially expressed in human bile, 18 up-regulated and 28 down-regulated. In the case of porcine bile, 32 proteins were differentially expressed of which 19 were up-regulated, and 13 were down-regulated. Functional classifications revealed that identified proteins participated in various biological functions including stress response, energy metabolism, membrane stability, motility, virulence and colonization. Selected genes were analyzed by RT-PCR to provide internal validation for the proteomic data as well as provide insight into specific expressions of motility, colonization and virulence genes of H. hepaticus in response to human or porcine bile.Overall, the data suggested that bile is an important factor that determines virulence, host adaptation, localization and colonization of specific niches within host environment.Helicobacter hepaticus belongs to the genus Helicobacter whose best known specie is the human gastric carcinogen Helicobacter pylori. Members of the genus are Gram-negative, microaerophilic bacillar bacteria that are classified either as gastric or enterohepatic species (EHS) depending on their target organs. H. hepaticus is the prototype EHS and the most studied species of the group. It was first isolated in 1992 from the liver specimen of laboratory mice suffering from chronic hepatic inflammation and liver cancer [1], and it is now known that the infection caused by the bacterium is widespread among mouse colonies worldwide [2-4]. In humans, H. hepaticus has been associated with hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) [5,6], cholelithiasis [7], and inflammatory bowel disease [4,8-10]. Experimental infection with the bacterium has been used as a model of microbial tumor promotion in the liver, colon and mammary glands [11-13], providing ample opportunity to elucidate specific relationships of this group of bacteria with t