Suwandi Abdulhadi, Alvarez Kris Gerard, Galeev Alibek, Steck Natalie, Riedel Christian U, Puente José Luis, Baines John F, Grassl Guntram A
Institute of Cell Biochemistry, Center of Biochemistry, Hannover Medical School, Hannover, Germany.
Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School and German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany.
Front Microbiol. 2022 Aug 11;13:980495. doi: 10.3389/fmicb.2022.980495. eCollection 2022.
Histo-blood group antigens in the intestinal mucosa play important roles in host-microbe interactions and modulate the susceptibility to enteric pathogens. The 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 expression is associated with increased susceptibility to infection, a murine model pathogen for human enteropathogenic We observed increased histopathological changes upon infection in mice lacking B4galnt2 compared to -expressing wild-type mice. In addition, wild-type mice cleared the infection faster than knockout mice. It is known that 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 deficient mice compared to sufficient mice. Adhesion assays using intestinal epithelial organoid-derived monolayers revealed higher adherence to cells lacking expression compared to wild-type cells which in turn was reduced in the absence of type I fimbriae. In summary, we show that expression modulates the susceptibility to infection, which is partly mediated by fimbriae-mannose interaction.
肠道黏膜中的组织血型抗原在宿主与微生物的相互作用中发挥重要作用，并调节对肠道病原体的易感性。该基因在包括人类在内的大多数哺乳动物的胃肠道中表达，编码一种β-1,4-N-乙酰半乳糖胺基转移酶，该酶通过将N-乙酰半乳糖胺（GalNAc）残基添加到前体分子上来催化Sd(a)和Cad血型抗原生物合成的最后一步。在我们的研究中，我们发现该基因表达缺失与对一种人类肠道致病性大肠杆菌的鼠模型病原体感染的易感性增加有关。与表达该基因的野生型小鼠相比，我们观察到缺乏B4galnt2的小鼠在感染后组织病理学变化增加。此外，野生型小鼠比基因敲除小鼠更快清除感染。已知该大肠杆菌利用其1型菌毛粘附亚基特异性结合黏膜细胞上的D-甘露糖残基。对肠上皮细胞的流式细胞术分析表明，与充足的小鼠相比，基因缺陷小鼠中不存在GalNAc修饰的聚糖，但甘露糖基化聚糖增加。使用肠上皮类器官衍生的单层进行的粘附试验显示，与野生型细胞相比，该大肠杆菌对缺乏该基因表达的细胞的粘附性更高，而在没有1型菌毛的情况下，这种粘附性会降低。总之，我们表明该基因表达调节对该大肠杆菌感染的易感性，这部分是由菌毛-甘露糖相互作用介导的。
