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The Role of Glycosylation in Host-Microbial Interactions

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 21131

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Special Issue Editors

Prof. Dr. Lokesh Joshi

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Guest Editor

Glycoscience Group, National University of Ireland Galway, Galway, Ireland
Interests: Glycosciences; Diagnostics; biomarkers; therapeutics; molecular biomimics
Special Issues, Collections and Topics in MDPI journals

Dr. Michelle Kilcoyne

E-Mail Website
Guest Editor

Carbohydrate Signalling Group, National University of Ireland Galway, Galway, Ireland
Interests: host-microbe interactions; immune response; bacterial polysaccharides and biofilms; and the application and development of carbohydrate analytical methods and platforms for analytics

Special Issue Information

Dear Colleagues,

Carbohydrates are ubiquitously present on all living cell surfaces and as major extracellular matrix components that play critical biological roles in human health and disease. Although many aspects of the field of glycoscience encompassing structural complexity and functional relevance are still not well understood, significant advances have been made since the turn of the century elucidating the central roles played by carbohydrate–protein interactions.

One major field of advance in glycoscience and its role in biology is in the domain of host–microbial interactions. Most microbial interactions with host surfaces are mediated by carbohydrate–protein interactions to establish pathogenic or commensal relationships. In addition to the roles identified in host–pathogen interactions, our understanding of the role of gastrointestinal tract mucosal surface in colonisation of the host gut by commensal microbiome is in its infancy. Mucins are the main components of host mucus, and mucin glycosylation functions as ligands for bacterial adhesins and as a source of microbial nutrients. Mucin glycosylation is very responsive to the immediate environment and varies depending on species, location in the body, hormonal status, inflammation, and presence of microbes. In addition, microbes can interact with the host via their surface glycosylation, and this may provide vaccine targets, e.g., bacterial capsular polysaccharides have been used as vaccines such as pneumococcal vaccines. Many factors, including diet, influence gut glycosylation and the microbial population and thus have an impact on their interactions and cross-talk, thus effecting human gut health and disease.

This Issue will elucidate the role of microbial or host glycosylation in host–microbe interactions in human health and disease.

Prof. Dr. Lokesh Joshi
Dr. Michelle Kilcoyne
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

glycosylation
carbohydrates
microbial
adhesion
mucin
receptors
infection
gastrointestinal tract
host–microbe interactions
commensal

Published Papers (6 papers)

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Research

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17 pages, 1310 KiB

Open AccessArticle

A Whey Fraction Rich in Immunoglobulin G Combined with Bifidobacterium longum subsp. infantis ATCC 15697 Exhibits Synergistic Effects against Campylobacter jejuni

by Erinn M. Quinn, Michelle Kilcoyne, Dan Walsh, Lokesh Joshi and Rita M. Hickey

Int. J. Mol. Sci. 2020, 21(13), 4632; https://doi.org/10.3390/ijms21134632 - 29 Jun 2020

Cited by 6 | Viewed by 2657

Abstract

Evidence that whey proteins and peptides have health benefits beyond basic infant nutrition has increased dramatically in recent years. Previously, we demonstrated that a whey-derived immunoglobulin G-enriched powder (IGEP) enhanced adhesion of Bifidobacterium longum subsp. infantis ATCC 15697 (B. infantis) to HT-29 cells. In this study, we investigated the synergistic effect of IGEP-treated B. infantis on preventing the attachment of highly invasive Campylobacter jejuni 81–176 (C. jejuni) to intestinal HT-29 cells. The combination decreased the adherence of C. jejuni to the HT-29 cells by an average of 48% compared to the control (non-IGEP-treated B. infantis). We also confirmed that treatment of IGEP with sodium metaperiodate, which disables the biological recognition of the conjugated oligosaccharides, reduced adhesion of B. infantis to the intestinal cells. Thus, glycosylation of the IGEP components may be important in enhancing B. infantis adhesion. Interestingly, an increased adhesion phenotype was not observed when B. infantis was treated with bovine serum-derived IgG, suggesting that bioactivity was unique to milk-derived immunoglobulin-rich powders. Notably, IGEP did not induce growth of B. infantis within a 24 hours incubation period, as demonstrated by growth curves and metabolite analysis. The current study provides insight into the functionality of bovine whey components and highlights their potential in positively impacting the development of a healthy microbiota. Full article

(This article belongs to the Special Issue The Role of Glycosylation in Host-Microbial Interactions)

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23 pages, 2840 KiB

Open AccessArticle

Glycomics Microarrays Reveal Differential In Situ Presentation of the Biofilm Polysaccharide Poly-N-acetylglucosamine on Acinetobacter baumannii and Staphylococcus aureus Cell Surfaces

by Andrea Flannery, Marie Le Berre, Gerald B. Pier, James P. O’Gara and Michelle Kilcoyne

Int. J. Mol. Sci. 2020, 21(7), 2465; https://doi.org/10.3390/ijms21072465 - 2 Apr 2020

Cited by 23 | Viewed by 4412

Abstract

The biofilm component poly-N-acetylglucosamine (PNAG) is an important virulence determinant in medical-device-related infections caused by ESKAPE group pathogens including Gram-positive Staphylococcus aureus and Gram-negative Acinetobacter baumannii. PNAG presentation on bacterial cell surfaces and its accessibility for host interactions are not fully understood. We employed a lectin microarray to examine PNAG surface presentation and interactions on methicillin-sensitive (MSSA) and methicillin-resistant S. aureus (MRSA) and a clinical A. baumannii isolate. Purified PNAG bound to wheatgerm agglutinin (WGA) and succinylated WGA (sWGA) lectins only. PNAG was the main accessible surface component on MSSA but was relatively inaccessible on the A. baumannii surface, where it modulated the presentation of other surface molecules. Carbohydrate microarrays demonstrated similar specificities of S. aureus and A. baumannii for their most intensely binding carbohydrates, including 3′ and 6′sialyllactose, but differences in moderately binding ligands, including blood groups A and B. An N-acetylglucosamine-binding lectin function which binds to PNAG identified on the A. baumannii cell surface may contribute to biofilm structure and PNAG surface presentation on A. baumannii. Overall, these data indicated differences in PNAG presentation and accessibility for interactions on Gram-positive and Gram-negative cell surfaces which may play an important role in biofilm-mediated pathogenesis. Full article

(This article belongs to the Special Issue The Role of Glycosylation in Host-Microbial Interactions)

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17 pages, 4797 KiB

Open AccessArticle

Region-Specific Sialylation Pattern of Prion Strains Provides Novel Insight into Prion Neurotropism

by Natallia Makarava, Jennifer Chen-Yu Chang and Ilia V. Baskakov

Int. J. Mol. Sci. 2020, 21(3), 828; https://doi.org/10.3390/ijms21030828 - 28 Jan 2020

Cited by 17 | Viewed by 2551

Abstract

Mammalian prions are unconventional infectious agents that invade and replicate in an organism by recruiting a normal form of a prion protein (PrP^C) and converting it into misfolded, disease-associated state referred to as PrP^Sc. PrP^C is posttranslationally modified with two N-linked glycans. Prion strains replicate by selecting substrates from a large pool of PrP^C sialoglycoforms expressed by a host. Brain regions have different vulnerability to prion infection, however, molecular mechanisms underlying selective vulnerability is not well understood. Toward addressing this question, the current study looked into a possibility that sialylation of PrP^Sc might be involved in defining selective vulnerability of brain regions. The current work found that in 22L -infected animals, PrP^Sc is indeed sialylated in a region dependent manner. PrP^Sc in hippocampus and cortex was more sialylated than PrP^Sc from thalamus and stem. Similar trends were also observed in brain materials from RML- and ME7-infected animals. The current study established that PrP^Sc sialylation status is indeed region-specific. Together with previous studies demonstrating that low sialylation status accelerates prion replication, this work suggests that high vulnerability of certain brain region to prion infection could be attributed to their low sialylation status. Full article

(This article belongs to the Special Issue The Role of Glycosylation in Host-Microbial Interactions)

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20 pages, 1940 KiB

Open AccessArticle

Receptor Heterodimerization and Co-Receptor Engagement in TLR2 Activation Induced by MIC1 and MIC4 from Toxoplasma gondii

by Flávia Costa Mendonça-Natividade, Carla Duque Lopes, Rafael Ricci-Azevedo, Aline Sardinha-Silva, Camila Figueiredo Pinzan, Ana Claudia Paiva Alegre-Maller, Lilian L. Nohara, Alan B. Carneiro, Ademilson Panunto-Castelo, Igor C. Almeida and Maria Cristina Roque-Barreira

Int. J. Mol. Sci. 2019, 20(20), 5001; https://doi.org/10.3390/ijms20205001 - 10 Oct 2019

Cited by 6 | Viewed by 3592

Abstract

The microneme organelles of Toxoplasma gondii tachyzoites release protein complexes (MICs), including one composed of the transmembrane protein MIC6 plus MIC1 and MIC4. In this complex, carbohydrate recognition domains of MIC1 and MIC4 are exposed and interact with terminal sialic acid and galactose residues, respectively, of host cell glycans. Recently, we demonstrated that MIC1 and MIC4 binding to the N-glycans of Toll-like receptor (TLR) 2 and TLR4 on phagocytes triggers cell activation and pro-inflammatory cytokine production. Herein, we investigated the requirement for TLR2 heterodimerization and co-receptors in MIC-induced responses, as well as the signaling molecules involved. We used MICs to stimulate macrophages and HEK293T cells transfected with TLR2 and TLR1 or TLR6, both with or without the co-receptors CD14 and CD36. Then, the cell responses were analyzed, including nuclear factor-kappa B (NF-κB) activation and cytokine production, which showed that (1) only TLR2, among the studied factors, is crucial for MIC-induced cell activation; (2) TLR2 heterodimerization augments, but is not critical for, activation; (3) CD14 and CD36 enhance the response to MIC stimulus; and (4) MICs activate cells through a transforming growth factor beta-activated kinase 1 (TAK1)-, mammalian p38 mitogen-activated protein kinase (p38)-, and NF-κB-dependent pathway. Remarkably, among the studied factors, the interaction of MIC1 and MIC4 with TLR2 N-glycans is sufficient to induce cell activation, which promotes host protection against T. gondii infection. Full article

(This article belongs to the Special Issue The Role of Glycosylation in Host-Microbial Interactions)

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Review

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26 pages, 1677 KiB

Open AccessReview

Host Synthesized Carbohydrate Antigens on Viral Glycoproteins as “Achilles’ Heel” of Viruses Contributing to Anti-Viral Immune Protection

by Uri Galili

Int. J. Mol. Sci. 2020, 21(18), 6702; https://doi.org/10.3390/ijms21186702 - 13 Sep 2020

Cited by 8 | Viewed by 3397

Abstract

The glycans on enveloped viruses are synthesized by host-cell machinery. Some of these glycans on zoonotic viruses of mammalian reservoirs are recognized by human natural antibodies that may protect against such viruses. These antibodies are produced mostly against carbohydrate antigens on gastrointestinal bacteria and fortuitously, they bind to carbohydrate antigens synthesized in other mammals, neutralize and destroy viruses presenting these antigens. Two such antibodies are: anti-Gal binding to α-gal epitopes synthesized in non-primate mammals, lemurs, and New World monkeys, and anti-N-glycolyl neuraminic acid (anti-Neu5Gc) binding to N-glycolyl-neuraminic acid (Neu5Gc) synthesized in apes, Old World monkeys, and many non-primate mammals. Anti-Gal appeared in Old World primates following accidental inactivation of the α1,3galactosyltransferase gene 20–30 million years ago. Anti-Neu5Gc appeared in hominins following the inactivation of the cytidine-monophosphate-N-acetyl-neuraminic acid hydroxylase gene, which led to the loss of Neu5Gc <6 million-years-ago. It is suggested that an epidemic of a lethal virus eliminated ancestral Old World-primates synthesizing α-gal epitopes, whereas few mutated offspring lacking α-gal epitopes and producing anti-Gal survived because anti-Gal destroyed viruses presenting α-gal epitopes, following replication in parental populations. Similarly, anti-Neu5Gc protected few mutated hominins lacking Neu5Gc in lethal virus epidemics that eliminated parental hominins synthesizing Neu5Gc. Since α-gal epitopes are presented on many zoonotic viruses it is suggested that vaccines elevating anti-Gal titers may be of protective significance in areas endemic for such zoonotic viruses. This protection would be during the non-primate mammal to human virus transmission, but not in subsequent human to human transmission where the virus presents human glycans. In addition, production of viral vaccines presenting multiple α-gal epitopes increases their immunogenicity because of effective anti-Gal-mediated targeting of vaccines to antigen presenting cells for extensive uptake of the vaccine by these cells. Full article

(This article belongs to the Special Issue The Role of Glycosylation in Host-Microbial Interactions)

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13 pages, 1485 KiB

Open AccessReview

Structure, Function, and Regulation of the Essential Virulence Factor Capsular Polysaccharide of Vibrio vulnificus

by Gregg S. Pettis and Aheli S. Mukerji

Int. J. Mol. Sci. 2020, 21(9), 3259; https://doi.org/10.3390/ijms21093259 - 5 May 2020

Cited by 26 | Viewed by 4148

Abstract

Vibrio vulnificus populates coastal waters around the world, where it exists freely or becomes concentrated in filter feeding mollusks. It also causes rapid and life-threatening sepsis and wound infections in humans. Of its many virulence factors, it is the V. vulnificus capsule, composed of capsular polysaccharide (CPS), that plays a critical role in evasion of the host innate immune system by conferring antiphagocytic ability and resistance to complement-mediated killing. CPS may also provoke a portion of the host inflammatory cytokine response to this bacterium. CPS production is biochemically and genetically diverse among strains of V. vulnificus, and the carbohydrate diversity of CPS is likely affected by horizontal gene transfer events that result in new combinations of biosynthetic genes. Phase variation between virulent encapsulated opaque colonial variants and attenuated translucent colonial variants, which have little or no CPS, is a common phenotype among strains of this species. One mechanism for generating acapsular variants likely involves homologous recombination between repeat sequences flanking the wzb phosphatase gene within the Group 1 CPS biosynthetic and transport operon. A considerable number of environmental, genetic, and regulatory factors have now been identified that affect CPS gene expression and CPS production in this pathogen. Full article

(This article belongs to the Special Issue The Role of Glycosylation in Host-Microbial Interactions)

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