Structural diversity and specific distribution of O-glycans in normal human mucins along the intestinal tract

Robbe, Catherine; Capon, Calliope; Coddeville, Bernadette; Michalski, Jean‐Claude

doi:10.1042/bj20040605

Cited by 317 publications

(331 citation statements)

References 45 publications

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“…Interestingly, a stretch of SpaC sequence (residue 137-262) is similar to the type A domain of the von Willebrand factor (vWFA), which is considered a prerequisite for the adherence of Streptococcus agalactiae pili to epithelial cells (33). Despite interacting primarily with human extracellular matrix proteins (34), a region of the vWFA domain (residue 201-299) demonstrates weak homology with a fucose-binding lectin domain, suggesting that the vWFA-like domain in SpaC may bind in a lectin-type manner, a distinct plausibility considering that heavily glycosylated mucin glycoproteins are the main component of mucus (35). Because the L. rhamnosus GG and LC705 genomes only encode a limited set of strain-specific adhesins, it is reasonable to speculate that the prolonged intestinal persistence of strain GG found during an intervention study (Fig.…”

Section: Discussionmentioning

confidence: 99%

Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein

Kankainen

Paulín

Tynkkynen

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

649

901

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To unravel the biological function of the widely used probiotic bacterium Lactobacillus rhamnosus GG, we compared its 3.0-Mbp genome sequence with the similarly sized genome of L. rhamnosus LC705, an adjunct starter culture exhibiting reduced binding to mucus. Both genomes demonstrated high sequence identity and synteny. However, for both strains, genomic islands, 5 in GG and 4 in LC705, punctuated the colinearity. A significant number of strain-specific genes were predicted in these islands (80 in GG and 72 in LC705). The GG-specific islands included genes coding for bacteriophage components, sugar metabolism and transport, and exopolysaccharide biosynthesis. One island only found in L. rhamnosus GG contained genes for 3 secreted LPXTG-like pilins (spaCBA) and a pilin-dedicated sortase. Using anti-SpaC antibodies, the physical presence of cell wall-bound pili was confirmed by immunoblotting. Immunogold electron microscopy showed that the SpaC pilin is located at the pilus tip but also sporadically throughout the structure. Moreover, the adherence of strain GG to human intestinal mucus was blocked by SpaC antiserum and abolished in a mutant carrying an inactivated spaC gene. Similarly, binding to mucus was demonstrated for the purified SpaC protein. We conclude that the presence of SpaC is essential for the mucus interaction of L. rhamnosus GG and likely explains its ability to persist in the human intestinal tract longer than LC705 during an intervention trial. The presence of mucus-binding pili on the surface of a nonpathogenic Gram-positive bacterial strain reveals a previously undescribed mechanism for the interaction of selected probiotic lactobacilli with host tissues.genome ͉ probiotics ͉ adhesion ͉ pilus ͉ lactic acid bacteria

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Section: Discussionmentioning

confidence: 99%

Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein

Kankainen

Paulín

Tynkkynen

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

649

901

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“…33-36 Unfortunately, the development of these antibodies into anti-cancer therapeutics has been quite challenging, because many Lewis antigens are also expressed in several types of normal tissues, particularly in the mucosa of human gastrointestinal tract in the form of O -linked glycans attached to the mucins. 37-48 For example, anti-Le y antibodies showed strong side effects including nausea and vomiting in Phase 1 clinical studies because the expression of Le y in the gastrointestinal tract 33 …”

Section: Protein Fucosylation In Mammalian Systemmentioning

confidence: 99%

The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity

Pereira

Chan

Lin

et al. 2018

mAbs

267

211

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Therapeutic monoclonal antibodies are the fastest growing class of biological therapeutics for the treatment of various cancers and inflammatory disorders. In cancer immunotherapy, some IgG1 antibodies rely on the Fc-mediated immune effector function, antibody-dependent cellular cytotoxicity (ADCC), as the major mode of action to deplete tumor cells. It is well-known that this effector function is modulated by the N-linked glycosylation in the Fc region of the antibody. In particular, absence of core fucose on the Fc N-glycan has been shown to increase IgG1 Fc binding affinity to the FcγRIIIa present on immune effector cells such as natural killer cells and lead to enhanced ADCC activity. As such, various strategies have focused on producing afucosylated antibodies to improve therapeutic efficacy. This review discusses the relevance of antibody core fucosylation to ADCC, different strategies to produce afucosylated antibodies, and an update of afucosylated antibody drugs currently undergoing clinical trials as well as those that have been approved.

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“…These glycan chains are highly heterogeneous in chain length and composition even at homeostasis. Importantly, glycan structure can be influenced during parasitic infections, which aids host protection against pathogenesis (which will be discussed further below) 33, 34, 35, 36…”

Section: Muc2 Biosynthesismentioning

confidence: 99%

A sticky end for gastrointestinal helminths; the role of the mucus barrier

Sharpe

Thornton

Grencis

2018

Parasite Immunology

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SummaryGastrointestinal (GI) nematodes are a group of successful multicellular parasites that have evolved to coexist within the intestinal niche of multiple species. It is estimated that over 10% of the world's population are chronically infected by GI nematodes, making this group of parasitic nematodes a major burden to global health. Despite the large number of affected individuals, there are few effective treatments to eradicate these infections. Research into GI nematode infections has primarily focused on defining the immunological and pathological consequences on host protection. One important but neglected aspect of host protection is mucus, and the concept that mucus is just a simple barrier is no longer tenable. In fact, mucus is a highly regulated and dynamic‐secreted matrix, underpinned by a physical hydrated network of highly glycosylated mucins, which is increasingly recognized to have a key protective role against GI nematode infections. Unravelling the complex interplay between mucins, the underlying epithelium and immune cells during infection are a major challenge and are required to fully define the protective role of the mucus barrier. This review summarizes the current state of knowledge on mucins and the mucus barrier during GI nematode infections, with particular focus on murine models of infection.

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Structural diversity and specific distribution of O-glycans in normal human mucins along the intestinal tract

Cited by 317 publications

References 45 publications

Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein

Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein

The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity

A sticky end for gastrointestinal helminths; the role of the mucus barrier

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