a changing gastric environment leads to adaptation of lipopolysaccharide variants in helicobacter pylori populations during colonization胃环境变化导致适应殖民期间幽门螺旋杆菌脂多糖变种的人群.pdfVIP

A Changing Gastric Environment Leads to Adaptation of Lipopolysaccharide Variants in Helicobacter pylori Populations during Colonization 1,2. ¨ 1,2. 1,2¤ ¨ 2 Anna Skoglund , Helene Kling Backhed , Christina Nilsson , Britta Bjorkholm , Staffan Normark1,2, Lars Engstrand1,2* 1 Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden, 2 Swedish Institute for Infectious Disease Control, Solna, Sweden Abstract The human gastric pathogen Helicobacter pylori colonizes the stomachs of half of the human population, and causes development of peptic ulcer disease and gastric adenocarcinoma. H. pylori-associated chronic atrophic gastritis (ChAG) with loss of the acid-producing parietal cells, is correlated with an increased risk for development of gastric adenocarinoma. The majority of H. pylori isolates produce lipopolysaccharides (LPS) decorated with human-related Lewis epitopes, which have been shown to phase-vary in response to different environmental conditions. We have characterized the adaptations of H. pylori LPS and Lewis antigen expression to varying gastric conditions; in H. pylori isolates from mice with low or high gastric pH, respectively; in 482 clinical isolates from healthy individuals and from individuals with ChAG obtained at two time points with a four-year interval between endoscopies; and finally in isolates grown at different pH in vitro. Here we show that the gastric environment can contribute to a switch in Lewis phenotype in the two experimental mouse models. The clinical isolates from different human individuals showed that intra-individual isolates varied in Lewis antigen expression although the LPS diversity was relatively stable within each individual over