Relationship Between Steroid Hormones and Helicobacter pylori

Helicobacter pylori is a Gram-negative microaerobic curved-rod possessing polar flagella as the motility organ. This bacterium colonizes human gastric epithelium and causes chronic gastritis and peptic ulcers (Graham, 1991; Warren & Marshall, 1983; Wyatt & Dixon, 1988). Via longer periods of colonization in the human stomach, it also contributes to the development of gastric cancer and marginal zone B-cell lymphoma (Forman, Eurogast Study Group, 1993; Wotherspoon et al., 1991). Approximately half of population in the world is infected with Helicobacter pylori, and the majority of infected persons develop atrophic gastritis with or without symptoms. Among Helicobacter pylori-infected individuals, about 10% persons develop gastric and duodenal ulcers, 1% to 3% persons develop gastric adenocarcinoma, and 0.1% or less person develops gastric mucosa-associated lymphoid tissue (MALT) lymphoma (Fukase et al., 2008; Peek & Blaser, 2002; Peek & Crabtree, 2006; Stolte et al., 2002; Uemura et al., 2001). The bacterial species belonging to the genus Helicobacter have a unique feature of freecholesterol (FC) assimilation into the membrane lipid compositions (Haque et al., 1995, 1996). Helicobacter pylori aggressively absorbs free-cholesterol supplemented to a medium, or extracts free-cholesterol from the lipid raft of epithelial cell membrane when the organism adhered onto the epithelial cell surface (Wunder et al., 2006). The free-cholesterol assimilated into the Helicobacter pylori membranes is glucosylated via the enzymatic action, and the organism utilizes as the membrane lipid components both free-cholesterol itself and the glucosylated cholesterols. Previous study by our group has identified the following three types of glucosyl cholesterols in the membrane lipid compositions of Helicobacter pylori (Hirai et al., 1995): cholesteryl--D-glucopyranoside (CGL), cholesteryl-6-O-tetradecanoyl-D-glucopyranoside (CAG), and cholesteryl-6-O-phosphatidyl--D-glucopyranoside (CPG). One of the enzymes involved in the biosynthesis of glucosyl cholesterols is HP0421 protein, a cholesterol -glucosyltransferase encoded by HP0421 gene in Helicobacter pylori (Lebrun et al., 2006). The HP0421 protein adopts as the glucose source a uridine diphosphate-glucose (UDP-Glc) and catalyzes the dehydration condensation reaction between a 1-hydroxyl (OH) group of D-glucose (Glc) molecule and a 3-OH group of free-cholesterol (FC) molecule, and thereby CGL is synthesized. The other enzymes involved in the biosynthesis of CAG and CPG have still not been identified (Fig. 1). Though it is almost special cases that bacterial species produce glucosyl sterols, plants and fungi universally produce various glucosyl sterols such as glucosyl sitosterol and glucosyl