AUTHOR=Suwandi Abdulhadi , Alvarez Kris Gerard , Galeev Alibek , Steck Natalie , Riedel Christian U. , Puente José Luis , Baines John F. , Grassl Guntram A. 

TITLE=B4galnt2-mediated host glycosylation influences the susceptibility to Citrobacter rodentium infection

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.980495

DOI=10.3389/fmicb.2022.980495

ISSN=1664-302X

ABSTRACT=<p>Histo-blood group antigens in the intestinal mucosa play important roles in host–microbe interactions and modulate the susceptibility to enteric pathogens. The <italic>B4galnt2</italic> gene, expressed in the GI tract of most mammals, including humans, encodes a beta-1,4-N-acetylgalactosaminyltransferase enzyme which catalyzes the last step in the biosynthesis of the Sd(a) and Cad blood group antigens by adding an N-acetylgalactosamine (GalNAc) residue to the precursor molecules. In our study, we found that loss of <italic>B4galnt2</italic> expression is associated with increased susceptibility to <italic>Citrobacter rodentium</italic> infection, a murine model pathogen for human enteropathogenic <italic>Escherichia coli.</italic> We observed increased histopathological changes upon <italic>C. rodentium</italic> infection in mice lacking B4galnt2 compared to <italic>B4galnt2</italic>-expressing wild-type mice. In addition, wild-type mice cleared the <italic>C. rodentium</italic> infection faster than <italic>B4galnt2<sup>−/−</sup></italic> knockout mice. It is known that <italic>C. rodentium</italic> uses its type 1 fimbriae adhesive subunit to bind specifically to D-mannose residues on mucosal cells. Flow cytometry analysis of intestinal epithelial cells showed the absence of GalNAc-modified glycans but an increase in mannosylated glycans in <italic>B4galnt2-</italic>deficient mice compared to <italic>B4galnt2-</italic>sufficient mice. Adhesion assays using intestinal epithelial organoid-derived monolayers revealed higher <italic>C. rodentium</italic> adherence to cells lacking <italic>B4galnt2</italic> expression compared to wild-type cells which in turn was reduced in the absence of type I fimbriae. In summary, we show that <italic>B4galnt2</italic> expression modulates the susceptibility to <italic>C. rodentium</italic> infection, which is partly mediated by fimbriae-mannose interaction.</p>