Std fimbriae-fucose interaction increases Salmonella-induced intestinal inflammation and prolongs colonization
García Pastor, Lucía
Boyle, Erin C.
Casadesús Pursals, Josep
Grassl, Guntram A.
|Department||Universidad de Sevilla. Departamento de Genética|
|Abstract||Expression of ABO and Lewis histo-blood group antigens by the gastrointestinal epithelium is governed by an α-1,2-fucosyltransferase enzyme encoded by the Fut2 gene. Alterations in mucin glycosylation have been associated ...
Expression of ABO and Lewis histo-blood group antigens by the gastrointestinal epithelium is governed by an α-1,2-fucosyltransferase enzyme encoded by the Fut2 gene. Alterations in mucin glycosylation have been associated with susceptibility to various bacterial and viral infections. Salmonella enterica serovar Typhimurium is a food-borne pathogen and a major cause of gastroenteritis. In order to determine the role of Fut2-dependent glycans in Salmonella-triggered intestinal inflammation, Fut2+/+ and Fut2-/- mice were orally infected with S. Typhimurium and bacterial colonization and intestinal inflammation were analyzed. Bacterial load in the intestine of Fut2-/- mice was significantly lower compared to Fut2+/+ mice. Analysis of histopathological changes revealed significantly lower levels of intestinal inflammation in Fut2-/- mice compared to Fut2+/+ mice and measurement of lipocalin-2 level in feces corroborated histopathological findings. Salmonella express fimbriae that assist in adherence of bacteria to host cells thereby facilitating their invasion. The std fimbrial operon of S. Typhimurium encodes the π-class Std fimbriae which bind terminal α(1,2)-fucose residues. An isogenic mutant of S. Typhimurium lacking Std fimbriae colonized Fut2+/+ and Fut2-/- mice to similar levels and resulted in similar intestinal inflammation. In vitro adhesion assays revealed that bacteria possessing Std fimbriae adhered significantly more to fucosylated cell lines or primary epithelial cells in comparison to cells lacking α(1,2)-fucose. Overall, these results indicate that Salmonella-triggered intestinal inflammation and colonization are dependent on Std-fucose interaction.
|Funding agencies||Deutsche Forschungsgemeinschaft / German Research Foundation (DFG)
German Federal Ministry of Education and Research (BMBF)
SFB 944 project P4
|Citation||Suwandi, A., Galeev, A., Riedel, R., Sharma, S., Seeger, K., Sterzenbach, T.,...,Grassl, G.A. (2019). Std fimbriae-fucose interaction increases Salmonella-induced intestinal inflammation and prolongs colonization. PLOS Pathogens, 15 (7), e1007915.|