How fucose of blood group glycotypes programs human gut microbiota

Kononova, S. V.

doi:10.1134/s0006297917090012

Cited by 8 publications

(6 citation statements)

References 144 publications

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“…While sialic acids confer a negative charge to the glycoconjugate, terminal fucose residues confer hydrophobicity, but both are associated with mucosal protection and their alteration may result in disease ( 72 , 75 ). Thus, human fucosyltransferases and their expression have been studied for their importance in inflammation, mucosal colonization, and host immune response modulation ( 83 , 84 ), and more recently, their importance for the maintenance of healthy gut microbiota profiles has been stressed out ( 85 , 86 ). In R gills, a moderate increase in Fuc terminal residues was observed in the lamellar goblet cells and those of the epithelium covering the proximal cartilage, and fucosyltransferase expression appeared upregulated in fish with high infection intensity ( Figures 2 , 5 ).…”

Section: Discussionmentioning

confidence: 99%

Mucosal affairs: glycosylation and expression changes of gill goblet cells and mucins in a fish–polyopisthocotylidan interaction

Riera-Ferrer,

Del Pozo,

Muñoz-Berruezo

et al. 2024

Front. Vet. Sci.

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IntroductionSecreted mucins are highly O-glycosylated glycoproteins produced by goblet cells in mucosal epithelia. They constitute the protective viscous gel layer overlying the epithelia and are involved in pathogen recognition, adhesion and expulsion. The gill polyopisthocotylidan ectoparasite Sparicotyle chrysophrii, feeds on gilthead seabream (Sparus aurata) blood eliciting severe anemia.MethodsControl unexposed and recipient (R) gill samples of gilthead seabream experimentally infected with S. chrysophrii were obtained at six consecutive times (0, 11, 20, 32, 41, and 61 days post-exposure (dpe)). In histological samples, goblet cell numbers and their intensity of lectin labelling was registered. Expression of nine mucin genes (muc2, muc2a, muc2b, muc5a/c, muc4, muc13, muc18, muc19, imuc) and three regulatory factors involved in goblet cell differentiation (hes1, elf3, agr2) was studied by qPCR. In addition, differential expression of glycosyltransferases and glycosidases was analyzed in silico from previously obtained RNAseq datasets of S. chrysophrii-infected gilthead seabream gills with two different infection intensities.Results and DiscussionIncreased goblet cell differentiation (up-regulated elf3 and agr2) leading to neutral goblet cell hyperplasia on gill lamellae of R fish gills was found from 32 dpe on, when adult parasite stages were first detected. At this time point, acute increased expression of both secreted (muc2a, muc2b, muc5a/c) and membrane-bound mucins (imuc, muc4, muc18) occurred in R gills. Mucins did not acidify during the course of infection, but their glycosylation pattern varied towards more complex glycoconjugates with sialylated, fucosylated and branched structures, according to lectin labelling and the shift of glycosyltransferase expression patterns. Gilthead seabream gill mucosal response against S. chrysophrii involved neutral mucus hypersecretion, which could contribute to worm expulsion and facilitate gas exchange to counterbalance parasite-induced hypoxia. Stress induced by the sparicotylosis condition seems to lead to changes in glycosylation characteristic of more structurally complex mucins.

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Section: Discussionmentioning

confidence: 99%

Mucosal affairs: glycosylation and expression changes of gill goblet cells and mucins in a fish–polyopisthocotylidan interaction

Riera-Ferrer,

Del Pozo,

Muñoz-Berruezo

et al. 2024

Front. Vet. Sci.

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“…Structural and functional studies are now starting to reveal insights into why individuals expressing different HBGAs are at an increased risk of infections such as those caused by Vibrio cholera , Pseudomonas aeruginosa , norovirus, rotavirus and Helicobacter pylori 17 , 28 . By developing Lewis antigen cell-based models of the human small intestine, as well as performing docking studies, we have further defined why HBGA Le a – expressing non-secretor ( FUT2 − / − ) individuals, or young children (<2 years of age) are more susceptible to ETEC expressing CFA/I, or other related CFs family members 5 , 6 , 8 , 28 . Subsequently, our understanding and characterisation of these host-pathogen binding patterns could represent a critical point at which the adherence of ETEC expressing CFA/I and related CF family members, can be prevented with vaccines and/or anti-infection therapeutics that block this interaction (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, we have also observed that Bangladeshi children with the Le(a+ b−) phenotype are more likely to be infected by ETEC expressing the colonisation factor antigen I (CFA/I) and the related ETEC CF family fimbriae or pili 6 . The likely explanation for this being, CFA/I could bind to Le a glycolipid structures present in the small intestinal mucosal layer of very young children (<2 years of age) and individuals with FUT2 non-secretor status 7 , 8 .…”

Section: Introductionmentioning

confidence: 99%

Glyco-engineered cell line and computational docking studies reveals enterotoxigenic Escherichia coli CFA/I fimbriae bind to Lewis a glycans

Mottram

Liu

Chavan

et al. 2018

Sci Rep

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We have previously reported clinical data to suggest that colonization factor I (CFA/I) fimbriae of enterotoxigenic Escherichia coli (ETEC) can bind to Lewis a (Lea), a glycan epitope ubiquitous in the small intestinal mucosa of young children (<2 years of age), and individuals with a genetic mutation of FUT2. To further elucidate the physiological binding properties of this interaction, we engineered Chinese Hamster Ovary (CHO-K1) cells to express Lea or Leb determinants on both N- and O-glycans. We used our glyco-engineered CHO-K1 cell lines to demonstrate that CfaB, the major subunit of ETEC CFA/I fimbriae, as well as four related ETEC fimbriae, bind more to our CHO-K1 cell-line expressing Lea, compared to cells carrying Leb or the CHO-K1 wild-type glycan phenotype. Furthermore, using in-silico docking analysis, we predict up to three amino acids (Glu25, Asn27, Thr29) found in the immunoglobulin (Ig)-like groove region of CfaB of CFA/I and related fimbriae, could be important for the preferential and higher affinity binding of CFA/I fimbriae to the potentially structurally flexible Lea glycan. These findings may lead to a better molecular understanding of ETEC pathogenesis, aiding in the development of vaccines and/or anti-infection therapeutics.

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“…Remarkably, the secretor status of the FUT2 gene was suggested as a close correlation with a variety of gastrointestinal diseases, including IBD (Tang et al, 2021 ), and diseases caused by viruses, mainly norovirus (Nov) (Lindesmith et al, 2003 ; Currier et al, 2015 ) and rotavirus (RV) (Galeev et al, 2021 ). In fact, the reason behind this phenotype determines the presence or absence of HBGA, which consists of an attachment site and a carbon source of intestinal microbiota (Tong et al, 2014 ; Kononova, 2017 ), and the major binding saccharide of some viruses, including NoV (Chen et al, 2011 ) and RV (Sharma et al, 2020 ). Recently, alteration of the composition and function of the gut microbiota, namely dysbiosis, which was suggested, may greatly contribute to the pathogenesis of IBD.…”

Section: The Biosynthesis Of Hbgamentioning

confidence: 99%

Fucosyltransferase 2: A Genetic Risk Factor for Intestinal Diseases

Zhang

et al. 2022

Front. Microbiol.

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The fucosyltransferase 2 gene (FUT2) mediates the synthesis of histoblood group antigens (HBGA) that occur in vivo from multiple organs, particularly on the surface of intestinal epithelial cells and body fluids. To date, many studies have demonstrated that the interaction of HBGA with the host microbiota is the cause of pathogenesis of intestinal diseases, making FUT2 non-secretor a risk factor for inflammatory bowel disease (IBD) due to the lack of HBGA. As HBGA also acts as an attachment site for norovirus (NoV) and rotavirus (RV), the non-secretor becomes a protective factor for both viral infections. In addition, the interaction of norovirus and rotavirus with symbiotic bacteria has been found to play an important role in regulating enteroviral infection in IBD. Given the current incomplete understanding of the complex phenomenon and the underlying pathogenesis of intestinal diseases such as IBD, it has recently been hypothesized that the FUT2 gene regulates intestinal bacteria through attachment sites, may help to unravel the role of FUT2 and intestinal flora in the mechanism of intestinal diseases in the future, and provide new ideas for the prevention and treatment of intestinal diseases through more in-depth studies.

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How fucose of blood group glycotypes programs human gut microbiota

Cited by 8 publications

References 144 publications

Mucosal affairs: glycosylation and expression changes of gill goblet cells and mucins in a fish–polyopisthocotylidan interaction

Mucosal affairs: glycosylation and expression changes of gill goblet cells and mucins in a fish–polyopisthocotylidan interaction

Glyco-engineered cell line and computational docking studies reveals enterotoxigenic Escherichia coli CFA/I fimbriae bind to Lewis a glycans

Fucosyltransferase 2: A Genetic Risk Factor for Intestinal Diseases

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