Ascaris lumbricoides and ticks associated with sensitization to galactose α1,3-galactose and elicitation of the alpha-gal syndrome.

BACKGROUND: IgE to galactose alpha-1,3 galactose (alpha-gal) causes alpha-gal syndrome (delayed anaphylaxis after ingestion of mammalian meat). Development of sensitization has been attributed to tick bites; however, the possible role of other parasites has not been well studied. OBJECTIVE: Our aims were to assess the presence, relative abundances, and site of localization of alpha-gal-containing proteins in common ectoparasites and endoparasites endemic in an area of high prevalence of alpha-gal syndrome, as well as to investigate the ability of ascaris antigens to elicit a reaction in a humanized rat basophil in vitro sensitization model. METHODS: Levels of total IgE, Ascaris-specific IgE, and alpha-gal IgE were measured in sera from patients with challenge-proven alpha-gal syndrome and from controls without allergy. The presence, concentration, and localization of alpha-gal in parasites were assessed by ELISA, Western blotting, and immunohistochemistry. The ability of Ascaris lumbricoides antigen to elicit IgE-dependent reactivity was demonstrated by using the RS-ATL8 basophil reporter system. RESULTS: Alpha-gal IgE level correlated with A lumbricoides-specific IgE level. Alpha-gal protein at 70 to 130 kDa was detected in A lumbricoides at concentrations higher than those found in Rhipicephalus evertsi and Amblyomma hebraeum ticks. Immunohistochemistry was used to localize alpha-gal in tick salivary acini and the helminth gut. Non-alpha-gal-containing A lumbricoides antigens activated RS-ATL8 basophils primed with serum from subjects with alpha-gal syndrome. CONCLUSION: We demonstrated the presence, relative abundances, and site of localization of alpha-gal-containing proteins in parasites. The activation of RS-ATL8 IgE reporter cells primed with serum from subjects with alpha-gal syndrome on exposure to non-alpha-gal-containing A lumbricoides proteins indicates a possible role of exposure to A lumbricoides in alpha-gal sensitization and clinical reactivity.

Transcriptomic Analysis of Glycosylation and Neuroregulatory Pathways in Rodent Models in Response to Psychedelic Molecules.

The potential for psychedelic molecules in impacting cognitive flexibility has long been supported and acknowledged across scientific reports. In the current study, an approach leveraging knowledge-based gene-set information analysis has been adopted to explore the potential impact of psychedelic molecules on both glycosylation, (a post-translational modifications (PTM)) and on neuro-regulatory pathways. Though limitations and restrictions rise from the scarcity of publicly available 'omics' data, targeted analysis enabled us to identify a number of key glycogenes (Hexb, Hs6st2, Col9a2, B3gat2, Mgat5, Bgn) involved the structural organization of extracellular matrix and neuroprotective factors (Kl, Pomc, Oxt, Gal, Avp, Cartpt) which play vital roles in neuron protection, development as well as synaptic stability. In response to psychedelic molecules, we found that these genes and associated pathways are transcriptional altered in rodent models. The approach used indicates the potential to exploit existing datasets for hypothesis generation and testing for the molecular processes which play a role in the physiological response to psychedelic molecule effects. These reported findings, which focused on alterations in glycogenes and neuro-regulatory factors may provide a novel range of biomarkers to track the beneficial, as well as potential toxicological effects of psychedelic molecules.

Systematic review of topical interventions for the management of odour in patients with chronic or malignant fungating wounds.

Chronic wounds adversely affect the quality of life of individuals and odour is a well-recognised associated factor. Odour can affect sleep, well-being, social interactions, diet and potentially wound healing. This systematic review aims to examine the effectiveness of topical interventions in the management of odour associated with chronic and malignant fungating wounds. A systematic review guided by PRISMA recommendations of randomised controlled trials where odour intensity/odour is the primary outcome was undertaken. Inclusion criteria were adults (18 years and over) with chronic venous, arterial, diabetic or pressure ulcers or with malignant fungating wounds where odour has been managed through topical application of pharmacological/non-pharmacological agents. Searches were conducted in CENTRAL, CINAHL, EMBASE, MEDLINE, Scopus, and Web of Science. Eligibility screening, risk of bias assessment and data extraction was completed by authors working independently. Searches retrieved 171 titles and abstracts (157 post de-duplication). Thirteen studies were retained for full text review of which five (n = 137 individuals) examining the following treatments remained: metronidazole (n = 4), silver (n = 1). Meta-analysis was not possible but individual studies suggest improved outcomes (i.e., reduced odour) using metronidazole. Treatment options to manage wound odour are limited and hampered by lack of clinical trials, small sample sizes, and absence of standardised outcomes and consistent measurement. Whereas metronidazole and silver may have a role in controlling wound odour, robust and well-designed interventions with rigorous procedures and standardised odour outcomes are necessary to evaluate their contribution.

Burkholderia cenocepacia BCAM2418-induced antibody inhibits bacterial adhesion, confers protection to infection and enables identification of host glycans as adhesin targets.

Trimeric Autotransporter Adhesins (TAA) found in Gram-negative bacteria play a key role in virulence. This is the case of Burkholderia cepacia complex (Bcc), a group of related bacteria able to cause infections in patients with cystic fibrosis. These bacteria use TAAs, among other virulence factors, to bind to host protein receptors and their carbohydrate ligands. Blocking such contacts is an attractive approach to inhibit Bcc infections. In this study, using an antibody produced against the TAA BCAM2418 from the epidemic strain Burkholderia cenocepacia K56-2, we were able to uncover its roles as an adhesin and the type of host glycan structures that serve as recognition targets. The neutralisation of BCAM2418 was found to cause a reduction in the adhesion of the bacteria to bronchial cells and mucins. Moreover, in vivo studies have shown that the anti-BCAM2418 antibody exerted an inhibitory effect during infection in Galleria mellonella. Finally, inferred by glycan arrays, we were able to predict for the first time, host glycan epitopes for a TAA. We show that BCAM2418 favoured binding to 3'sialyl-3-fucosyllactose, histo-blood group A, α-(1,2)-linked Fuc-containing structures, Lewis structures and GM1 gangliosides. In addition, the glycan microarrays demonstrated similar specificities of Burkholderia species for their most intensely binding carbohydrates.

Symposium review: Dairy-derived oligosaccharides-Their influence on host-microbe interactions in the gastrointestinal tract of infants.

Oligosaccharides are the third most abundant component in human milk. It is widely accepted that they play several important protective, physiological, and biological roles, including selective growth stimulation of beneficial gut microbiota, inhibition of pathogen adhesion, and immune modulation. However, until recently, very few commercial products on the market have capitalized on these functions. This is mainly because the quantities of human milk oligosaccharides required for clinical trials have been unavailable. Recently, clinical studies have tested the potential beneficial effects of feeding infants formula containing 2'-fucosyllactose, which is the most abundant oligosaccharide in human milk. These studies have opened this field for further well-designed studies, which are required to fully understand the role of human milk oligosaccharides. However, one of the most striking features of human milk is its diversity of oligosaccharides, with over 200 identified to date. It may be that a mixture of oligosaccharides is even more beneficial to infants than a single structure. For this reason, the milk of domestic animals has become a focal point in recent years as an alternative source of complex oligosaccharides with associated biological activity. This review will focus specifically on free oligosaccharides found in bovine and caprine milk and the biological roles associated with such structures. These dairy streams are ideal sources of oligosaccharides, given their wide availability and use in so many regularly consumed dairy products. The aim of this review was to provide an overview of research into the functional role of bovine and caprine milk oligosaccharides in host-microbial interactions in the gut and provide current knowledge related to the isolation of oligosaccharides as ingredients for incorporation in functional or medical foods.

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

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.

Structure and N-acetylglucosamine binding of the distal domain of mouse adenovirus 2 fibre.

Murine adenovirus 2 (MAdV-2) infects cells of the mouse gastrointestinal tract. Like human adenoviruses, it is a member of the genus Mastadenovirus, family Adenoviridae. The MAdV-2 genome has a single fibre gene that expresses a 787 residue-long protein. Through analogy to other adenovirus fibre proteins, it is expected that the carboxy-terminal virus-distal head domain of the fibre is responsible for binding to the host cell, although the natural receptor is unknown. The putative head domain has little sequence identity to adenovirus fibres of known structure. In this report, we present high-resolution crystal structures of the carboxy-terminal part of the MAdV-2 fibre. The structures reveal a domain with the typical adenovirus fibre head topology and a domain containing two triple ß-spiral repeats of the shaft domain. Through glycan microarray profiling, saturation transfer difference nuclear magnetic resonance spectroscopy, isothermal titration calorimetry and site-directed mutagenesis, we show that the fibre specifically binds to the monosaccharide N-acetylglucosamine (GlcNAc). The crystal structure of the complex reveals that GlcNAc binds between the AB and CD loops at the top of each of the three monomers of the MAdV-2 fibre head. However, infection competition assays show that soluble GlcNAc monosaccharide and natural GlcNAc-containing polymers do not inhibit infection by MAdV-2. Furthermore, site-directed mutation of the GlcNAc-binding residues does not prevent the inhibition of infection by soluble fibre protein. On the other hand, we show that the MAdV-2 fibre protein binds GlcNAc-containing mucin glycans, which suggests that the MAdV-2 fibre protein may play a role in viral mucin penetration in the mouse gut.

Advances in analytical methodologies to guide bioprocess engineering for bio-therapeutics.

This study was performed to monitor the glycoform distribution of a recombinant antibody fusion protein expressed in CHO cells over the course of fed-batch bioreactor runs using high-throughput methods to accurately determine the glycosylation status of the cell culture and its product. Three different bioreactors running similar conditions were analysed at the same five time-points using the advanced methods described here. N-glycans from cell and secreted glycoproteins from CHO cells were analysed by HILIC-UPLC and MS, and the total glycosylation (both N- and O-linked glycans) secreted from the CHO cells were analysed by lectin microarrays. Cell glycoproteins contained mostly high mannose type N-linked glycans with some complex glycans; sialic acid was α-(2,3)-linked, galactose ß-(1,4)-linked, with core fucose. Glycans attached to secreted glycoproteins were mostly complex with sialic acid α-(2,3)-linked, galactose ß-(1,4)-linked, with mostly core fucose. There were no significant differences noted among the bioreactors in either the cell pellets or supernatants using the HILIC-UPLC method and only minor differences at the early time-points of days 1 and 3 by the lectin microarray method. In comparing different time-points, significant decreases in sialylation and branching with time were observed for glycans attached to both cell and secreted glycoproteins. Additionally, there was a significant decrease over time in high mannose type N-glycans from the cell glycoproteins. A combination of the complementary methods HILIC-UPLC and lectin microarrays could provide a powerful and rapid HTP profiling tool capable of yielding qualitative and quantitative data for a defined biopharmaceutical process, which would allow valuable near 'real-time' monitoring of the biopharmaceutical product.

Exploitation of SPR to Investigate the Importance of Glycan Chains in the Interaction between Lactoferrin and Bacteria.

Bovine lactoferrin (LF) has been shown to prevent adhesion to and invasion of mammalian cell lines by pathogenic bacteria, with evidence for direct bacterial binding by the milk glycoprotein. However, the glycosylation pattern of LF changes over the lactation cycle. In this study, we aim to investigate the effect that this variation has on the milk glycoprotein's ability to interact with pathogens. Surface plasmon resonance technology was employed to compare the binding of LF from colostrum (early lactation) and mature milk (late lactation) to a panel of pathogenic bacteria (Staphylococcus aureus, Escherichia coli, Cronobacter sakazakii, Streptococcus pneumoniae, Pseudomonas aeruginosa, Listeria monocytogenes and Salmonella typhimurium). Novel interactions with LF were identified for C. sakazakii, S. pneumoniae and P. aeruginosa with the highest binding ability observed for mature milk LF in all cases, with the exception of S. typhimurium. The difference in bacterial binding observed may be as a result of the varying glycosylation profiles. This work demonstrates the potential of LF as a functional food ingredient to prevent bacterial infection.

The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma.

Glycosylation is a stepwise procedure of covalent attachment of oligosaccharide chains to proteins or lipids, and alterations in this process, especially increased sialylation, have been associated with malignant transformation and metastasis. The role of altered sialylation in multiple myeloma (MM) cell trafficking has not been previously investigated. In the present study we identified high expression of ß-galactoside α-2,3-sialyltransferase, ST3GAL6, in MM cell lines and patients. This gene plays a key role in selectin ligand synthesis in humans through the generation of functional sialyl Lewis X. In MRC IX patients, high expression of this gene is associated with inferior overall survival. In this study we demonstrate that knockdown of ST3GAL6 results in a significant reduction in levels of α-2,3-linked sialic acid on the surface of MM cells with an associated significant reduction in adhesion to MM bone marrow stromal cells and fibronectin along with reduced transendothelial migration in vitro. In support of our in vitro findings, we demonstrate significantly reduced homing and engraftment of ST3GAL6 knockdown MM cells to the bone marrow niche in vivo, along with decreased tumor burden and prolonged survival. This study points to the importance of altered glycosylation, particularly sialylation, in MM cell adhesion and migration.

GlycoGAIT: A web database to browse glycogenes and lectins under gastric inflammatory diseases.

The perplexing nature of dynamic glycosylation modification plays imperative role in determining the regulatory role of key glycoconjugates involved in immune system. Systematic analysis of change in expression pattern of glycogenes and lectins can bring in a comprehensive understanding of genetic basis of the glycobiological changes occurring in pathological condition. Advancement in the field of glycobiology has capacitated the process of linking gene expression changes of glycogenes with its biological function. This instigated us to systematically analyze changes in expression patterns focusing on glycome genomics under diverse gastrointestinal immune dysfunction background. To necessitate this, as a pilot project, we carefully integrated several publically available databases to construct a glycosylation process associated gene set as well as public expression microarray data associated with gastrointestinal infections into an online database called Glycosylation and Gut Associated Immune Tolerance (GlycoGAIT). Currently the database comprises of 548 well characterized genes belonging to glycogenes and lectins along with gene expression data obtained from human biopsy samples under both H. pylori infection and inflammatory bowel disease (IBD) condition. The user-friendly interface enables the users to quickly compare and interpret changes in expression patterns of glycome genomics under different gut associated inflammatory conditions. The database is available online at: https://apps.connexios.com/glycogait/.

The Role of Oligosaccharides in Host-Microbial Interactions for Human Health.

Milk oligosaccharides have many associated bioactivities which can contribute to human health and offer protective properties to the host. Such bioactivities include anti-infective properties whereby oligosaccharides interact with bacterial cells and prevent adhesion to the host and subsequent colonization. Milk oligosaccharides have also been shown to alter the glycosylation of intestinal cells, leading to a reduction in pathogenic colonization. In addition, these sugars promote adhesion of commensal bacterial strains to host cells as well as possessing the ability to alter mucin expression in intestinal cells and improve barrier function. The ability of milk oligosaccharides to alter the transcriptome of both commensal bacterial strains and intestinal epithelial cells has also been revealed, indicating the potential of many cell types to detect the presence of milk oligosaccharides and respond accordingly at the genetic level. Interestingly, domestic animal milk may provide a bioactive source of oligosaccharides for formula supplementation with the aim of emulating the gold standard that is human milk. Overall, this review highlights the ability of milk oligosaccharides to promote health in a variety of ways, for example, through direct bacterial interactions, immunomodulatory activities, promotion of gut barrier function, and induction of protective transcriptional responses.

Structural and functional characteristics of bovine milk protein glycosylation.

Most secreted and cell membrane proteins in mammals are glycosylated. Many of these glycoproteins are also prevalent in milk and play key roles in the biomodulatory properties of milk and ultimately in determining milk's nutritional quality. Although a significant amount of information exists on the types and roles of free oligosaccharides in milk, very little is known about the glycans associated with milk glycoproteins, in particular, the biological properties that are linked to their presence. The main glycoproteins found in bovine milk are lactoferrin, the immunoglobulins, glycomacropeptide, a glycopeptide derived from κ-casein, and the glycoproteins of the milk fat globule membrane. Here, we review the glycoproteins present in bovine milk, the information currently available on their glycosylation and the biological significance of their oligosaccharide chains.

Cross-platform comparison of glycan microarray formats.

Carbohydrates participate in almost every aspect of biology from protein sorting to modulating cell differentiation and cell-cell interactions. To date, the majority of data gathered on glycan expression has been obtained via analysis with either anti-glycan antibodies or lectins. A detailed understanding of the specificities of these reagents is critical to the analysis of carbohydrates in biological systems. Glycan microarrays are increasingly used to determine the binding specificity of glycan-binding proteins (GBPs). In this study, six different glycan microarray platforms with different modes of glycan presentation were compared using five well-known lectins; concanavalin A, Helix pomatia agglutinin, Maackia amurensis lectin I, Sambucus nigra agglutinin and wheat germ agglutinin. A new method (universal threshold) was developed to facilitate systematic comparisons across distinct array platforms. The strongest binders of each lectin were identified using the universal threshold across all platforms while identification of weaker binders was influenced by platform-specific factors including presentation of determinants, array composition and self-reported thresholding methods. This work compiles a rich dataset for comparative analysis of glycan array platforms and has important implications for the implementation of microarrays in the characterization of GBPs.

Cross-feeding by Bifidobacterium breve UCC2003 during co-cultivation with Bifidobacterium bifidum PRL2010 in a mucin-based medium.

BACKGROUND: Bifidobacteria constitute a specific group of commensal bacteria that commonly inhabit the mammalian gastrointestinal tract. Bifidobacterium breve UCC2003 was previously shown to utilize a variety of plant/diet/host-derived carbohydrates, including cellodextrin, starch and galactan, as well as the mucin and HMO-derived monosaccharide, sialic acid. In the current study, we investigated the ability of this strain to utilize parts of a host-derived source of carbohydrate, namely the mucin glycoprotein, when grown in co-culture with the mucin-degrading Bifidobacterium bifidum PRL2010. RESULTS: B. breve UCC2003 was shown to exhibit growth properties in a mucin-based medium, but only when grown in the presence of B. bifidum PRL2010, which is known to metabolize mucin. A combination of HPAEC-PAD and transcriptome analyses identified some of the possible monosaccharides and oligosaccharides which support this enhanced co-cultivation growth/viability phenotype. CONCLUSION: This study describes the potential existence of a gut commensal relationship between two bifidobacterial species. We demonstrate the in vitro ability of B. breve UCC2003 to cross-feed on sugars released by the mucin-degrading activity of B. bifidum PRL2010, thus advancing our knowledge on the metabolic adaptability which allows the former strain to colonize the (infant) gut by its extensive metabolic abilities to (co-)utilize available carbohydrate sources.

Donor bone marrow-derived dendritic cells prolong corneal allograft survival and promote an intragraft immunoregulatory milieu.

Investigations into cell therapies for application in organ transplantation have grown. Here, we describe the ex vivo generation of donor bone marrow-derived dendritic cells (BMDCs) and glucocorticoid-treated BMDCs with potent immunomodulatory properties for application in allogeneic transplantation. BMDCs were treated with dexamethasone (Dexa) to induce an immature, maturation-resistant phenotype. BMDC and Dexa BMDC phenotype, antigen presenting cell function, and immunomodulatory properties were fully characterized. Both populations display significant immunomodulatory properties, including, but not limited to, a significant increase in mRNA expression of programmed death-ligand 1 and indoleamine 2,3-dioxygenase. BMDCs and Dexa BMDCs display a profound impaired capacity to stimulate allogeneic lymphocytes. Moreover, in a fully MHC I/II mismatched rat corneal transplantation model, injection of donor-derived, untreated BMDC or Dexa BMDCs (1 × 10(6) cells, day -7) significantly prolonged corneal allograft survival without the need for additional immunosuppression. Although neovascularization was not reduced and evidence of donor-specific alloantibody response was detected, a significant reduction in allograft cellular infiltration combined with a significant increase in the ratio of intragraft FoxP3-expressing regulatory cells was observed. Our comprehensive analysis demonstrates the novel cellular therapeutic approach and significant effect of donor-derived, untreated BMDCs and Dexa BMDCs in preventing corneal allograft rejection.

Divergent mechanisms of interaction of Helicobacter pylori and Campylobacter jejuni with mucus and mucins.

Helicobacter pylori and Campylobacter jejuni colonize the stomach and intestinal mucus, respectively. Using a combination of mucus-secreting cells, purified mucins, and a novel mucin microarray platform, we examined the interactions of these two organisms with mucus and mucins. H. pylori and C. jejuni bound to distinctly different mucins. C. jejuni displayed a striking tropism for chicken gastrointestinal mucins compared to mucins from other animals and preferentially bound mucins from specific avian intestinal sites (in order of descending preference: the large intestine, proximal small intestine, and cecum). H. pylori bound to a number of animal mucins, including porcine stomach mucin, but with less avidity than that of C. jejuni for chicken mucin. The strengths of interaction of various wild-type strains of H. pylori with different animal mucins were comparable, even though they did not all express the same adhesins. The production of mucus by HT29-MTX-E12 cells promoted higher levels of infection by C. jejuni and H. pylori than those for the non-mucus-producing parental cell lines. Both C. jejuni and H. pylori bound to HT29-MTX-E12 mucus, and while both organisms bound to glycosylated epitopes in the glycolipid fraction of the mucus, only C. jejuni bound to purified mucin. This study highlights the role of mucus in promoting bacterial infection and emphasizes the potential for even closely related bacteria to interact with mucus in different ways to establish successful infections.

Development of a convenient competitive ELISA for the detection of the free and protein-bound nonhuman galactosyl-α-(1,3)-galactose epitope based on highly specific chicken single-chain antibody variable-region fragments.

The presence of the nonhuman galactosyl-α-(1,3)-galactose (Gal-α-(1,3)-Gal) carbohydrate epitope on a number of recombinant therapeutic proteins has recently been reported, renewing interest in this immunogenic carbohydrate epitope. It is well-known that this motif is the primary contributing factor in hyperacute rejection of porcine organ xenograft, due to the existence of natural antibodies against this epitope in human serum. Though the number of epitopes on recombinant glycoproteins may be low when compared directly to whole tissue, circulating anti-Gal-α-R immunoglobulins can still induce anaphylaxis. Therefore, there is a need for rapid and convenient methods for detection and monitoring of this epitope in biopharmaceuticals produced in recombinant mammalian systems. To this end, we have generated immune-challenged chicken single-chain antibody variable-region fragment (scFv) libraries targeting the Gal-α-(1,3)-Gal motif and have selected a panel of scFv's that bind the target. We have used one of these antibodies to develop a competitive ELISA for both free and protein-bound Gal-α-(1,3)-Gal and have demonstrated that the ELISA is specific for the target and can be used to determine the loading of the target on glycoproteins. This competitive ELISA will provide a convenient method of detecting and quantifying Gal-α-(1,3)-Gal on therapeutic glycoproteins.

SugarBind database (SugarBindDB): a resource of pathogen lectins and corresponding glycan targets.

SugarBindDB lists pathogen and biotoxin lectins and their carbohydrate ligands in a searchable format. Information is collected from articles published in peer-reviewed scientific journals. Help files guide the user through the search process and provide a review of structures and names of sugars that appear in human oligosaccharides. Glycans are written in the condensed form of the carbohydrate nomenclature system developed by the International Union of Pure and Applied Chemistry (IUPAC). Since its online publication by The MITRE Corporation in 2005, the database has served as a resource for research on the glycobiology of infectious disease. SugarBindDB is currently hosted by the Swiss Institute of Bioinformatics on the ExPASy server and will be enhanced and linked to related resources as part of the wider UniCarbKB initiative. Enhancements will include the option to display glycans in a variety of formats, including modified 2D condensed IUPAC and symbolic nomenclature.

The MSHA pilus of Vibrio parahaemolyticus has lectin functionality and enables TTSS-mediated pathogenicity.

Vibrio parahaemolyticus is a seafood-borne pathogen which causes acute inflammatory gastroenteritis--a process which is mediated by the translocation of type three secretion system effector proteins. The molecular interactions governing colonization of the intestinal epithelium by this pathogen remain poorly understood. The mannose-sensitive haemagglutinin (MSHA) pilus was identified in this study as a significant factor in bacterial-host cell adherence and subsequent pathogenesis towards Caco-2 human intestinal epithelial cells. Deletion of essential components of the MSHA pilus resulted in a 60% decrease in adherence and a similar reduction in bacterial uptake by human intestinal cells. The diminished adherence of MSHA mutants correlated with significant decreases in V. parahaemolyticus-induced Caco-2 cell lysis, cell rounding and IL-8 secretion. Glycan array comparison between the V. parahaemolyticus wild type and MSHA deficient mutants identified lectin functionality for the MSHA pilus with specificity towards the fucosylated blood group oligosaccharide antigens Lewis A and X and blood groups A and B. The MSHA pilus also exhibited high affinity for the structurally related asialo-GM1 ganglioside, lacto-N-fucopentaose I and lacto-N-difucohexaose I. We hypothesize that these glycans act as receptors for the MSHA pilus in the gastrointestinal tract, thereby facilitating efficient colonization of the intestinal epithelium by V. parahaemolyticus.