B4galnt2-mediated host glycosylation influences the susceptibility to Citrobacter rodentium infection
Histo-blood group antigens in the intestinal mucosa play important roles in host–microbe interactions and modulate the susceptibility to enteric pathogens. The B4galnt2 gene, expressed in the GI tract of most mammals, including humans, encodes a beta-1,4-N-acetylgalactosaminyltransferase enzyme whic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.980495/full |
| _version_ | 1811217201313611776 |
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| author | Abdulhadi Suwandi Abdulhadi Suwandi Kris Gerard Alvarez Alibek Galeev Alibek Galeev Natalie Steck Christian U. Riedel José Luis Puente John F. Baines John F. Baines Guntram A. Grassl |
| author_facet | Abdulhadi Suwandi Abdulhadi Suwandi Kris Gerard Alvarez Alibek Galeev Alibek Galeev Natalie Steck Christian U. Riedel José Luis Puente John F. Baines John F. Baines Guntram A. Grassl |
| author_sort | Abdulhadi Suwandi |
| collection | DOAJ |
| description | Histo-blood group antigens in the intestinal mucosa play important roles in host–microbe interactions and modulate the susceptibility to enteric pathogens. The B4galnt2 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 B4galnt2 expression is associated with increased susceptibility to Citrobacter rodentium infection, a murine model pathogen for human enteropathogenic Escherichia coli. We observed increased histopathological changes upon C. rodentium infection in mice lacking B4galnt2 compared to B4galnt2-expressing wild-type mice. In addition, wild-type mice cleared the C. rodentium infection faster than B4galnt2−/− knockout mice. It is known that C. rodentium 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 B4galnt2-deficient mice compared to B4galnt2-sufficient mice. Adhesion assays using intestinal epithelial organoid-derived monolayers revealed higher C. rodentium adherence to cells lacking B4galnt2 expression compared to wild-type cells which in turn was reduced in the absence of type I fimbriae. In summary, we show that B4galnt2 expression modulates the susceptibility to C. rodentium infection, which is partly mediated by fimbriae-mannose interaction. |
| first_indexed | 2024-04-12T06:51:25Z |
| format | Article |
| id | doaj.art-4eb77221e7ab4f0689a9d8a66d6b63f0 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T06:51:25Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-4eb77221e7ab4f0689a9d8a66d6b63f02022-12-22T03:43:20ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-08-011310.3389/fmicb.2022.980495980495B4galnt2-mediated host glycosylation influences the susceptibility to Citrobacter rodentium infectionAbdulhadi Suwandi0Abdulhadi Suwandi1Kris Gerard Alvarez2Alibek Galeev3Alibek Galeev4Natalie Steck5Christian U. Riedel6José Luis Puente7John F. Baines8John F. Baines9Guntram A. Grassl10Institute of Cell Biochemistry, Center of Biochemistry, Hannover Medical School, Hannover, GermanyInstitute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School and German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, GermanyInstitute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School and German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, GermanySection of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, GermanyMax Planck Institute for Evolutionary Biology, Plön, GermanySection of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, GermanyInstitute of Microbiology and Biotechnology, University of Ulm, Ulm, GermanyDepartamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, MexicoSection of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Kiel, GermanyMax Planck Institute for Evolutionary Biology, Plön, GermanyInstitute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School and German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, GermanyHisto-blood group antigens in the intestinal mucosa play important roles in host–microbe interactions and modulate the susceptibility to enteric pathogens. The B4galnt2 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 B4galnt2 expression is associated with increased susceptibility to Citrobacter rodentium infection, a murine model pathogen for human enteropathogenic Escherichia coli. We observed increased histopathological changes upon C. rodentium infection in mice lacking B4galnt2 compared to B4galnt2-expressing wild-type mice. In addition, wild-type mice cleared the C. rodentium infection faster than B4galnt2−/− knockout mice. It is known that C. rodentium 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 B4galnt2-deficient mice compared to B4galnt2-sufficient mice. Adhesion assays using intestinal epithelial organoid-derived monolayers revealed higher C. rodentium adherence to cells lacking B4galnt2 expression compared to wild-type cells which in turn was reduced in the absence of type I fimbriae. In summary, we show that B4galnt2 expression modulates the susceptibility to C. rodentium infection, which is partly mediated by fimbriae-mannose interaction.https://www.frontiersin.org/articles/10.3389/fmicb.2022.980495/fullB4galnt2Citrobacterintestinal inflammationintestinal glycansinfectious colitisgut colonization |
| spellingShingle | Abdulhadi Suwandi Abdulhadi Suwandi Kris Gerard Alvarez Alibek Galeev Alibek Galeev Natalie Steck Christian U. Riedel José Luis Puente John F. Baines John F. Baines Guntram A. Grassl B4galnt2-mediated host glycosylation influences the susceptibility to Citrobacter rodentium infection Frontiers in Microbiology B4galnt2 Citrobacter intestinal inflammation intestinal glycans infectious colitis gut colonization |
| title | B4galnt2-mediated host glycosylation influences the susceptibility to Citrobacter rodentium infection |
| title_full | B4galnt2-mediated host glycosylation influences the susceptibility to Citrobacter rodentium infection |
| title_fullStr | B4galnt2-mediated host glycosylation influences the susceptibility to Citrobacter rodentium infection |
| title_full_unstemmed | B4galnt2-mediated host glycosylation influences the susceptibility to Citrobacter rodentium infection |
| title_short | B4galnt2-mediated host glycosylation influences the susceptibility to Citrobacter rodentium infection |
| title_sort | b4galnt2 mediated host glycosylation influences the susceptibility to citrobacter rodentium infection |
| topic | B4galnt2 Citrobacter intestinal inflammation intestinal glycans infectious colitis gut colonization |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.980495/full |
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