Std fimbriae-fucose interaction increases Salmonella-induced intestinal inflammation and prolongs colonization.

Abdulhadi Suwandi,Samriti Sharma,Torsten Sterzenbach,Lucía García Pastor,John F Baines,Michael Hensel,Guntram A Grassl,Alibek Galeev,Ohad Gal-Mor,René Riedel,Erin C Boyle,Josep Casadesús,Katrin Seeger,Andreas J Baumler

doi:10.1371/journal.ppat.1007915

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 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.

Highlights

Glycosylation is an important type of post-translational modification of proteins and lipids and is involved in the regulation of a wide range of processes at the cellular and molecular level
We show that Salmonella expresses Std fimbriae in the gastrointestinal tract in vivo and exploit Std fimbriae to bind fucosylated structures in the mucus and on the intestinal epithelium
We demonstrate that the Std fimbriae-fucose interaction is necessary for bacterial colonization of the intestine and for triggering intestinal inflammation

Summary

Introduction

Glycosylation is an important type of post-translational modification of proteins and lipids and is involved in the regulation of a wide range of processes at the cellular and molecular level. The mucosal surface is characterized by a heavily glycosylated mucus layer produced by goblet cells as well as membrane-bound glycosylated proteins and lipids that form them [2]. These glycoconjugates can be utilized by intestinal commensal bacteria and pathogens as molecular attachment sites or as nutrients [3]. The non-secretor phenotype is associated with an increased risk to develop chronic inflammatory bowel diseases [10] This is possibly due to the altered composition of the intestinal microbiota, which may in turn influence the capacity of pathogenic bacteria to bind to host mucosal surface structures [11]

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