Glycopeptide antibiotics are regularly used in ophthalmology to treat infections of Gram-positive bacteria. Aggregative interactions of antibiotics with mucins however can lead to long exposure and increases the risk of resistant species. This study focuses on the evaluation of potential interactions of the last line of defence glycopeptide antibiotic teicoplanin with an ocular mucin model using precision matrix free hydrodynamic and microscopic techniques: sedimentation velocity in the analytical ultracentrifuge (SV-AUC), dynamic light scattering (DLS) and atomic force microscopy (AFM).
View Article and Find Full Text PDFThe natural glycopeptide antibiotic teicoplanin is used for the treatment of serious Gram-positive related bacterial infections and can be administered intravenously, intramuscularly, topically (ocular infections), or orally. It has also been considered for targeting viral infection by SARS-CoV-2. The hydrodynamic properties of teicoplanin A2 (M = 1880 g/mol) were examined in phosphate chloride buffer (pH 6.
View Article and Find Full Text PDFUbiquitous occurrence in Nature, abundant presence at strategically important places such as the cell surface and dynamic shifts in their profile by diverse molecular switches qualifies the glycans to serve as versatile biochemical signals. However, their exceptional structural complexity often prevents one noting how simple the rules of objective-driven assembly of glycan-encoded messages are. This review is intended to provide a tutorial for a broad readership.
View Article and Find Full Text PDFGlycoproteins are major players in the mucus protective barrier in the gastrointestinal and other mucosal surfaces. In particular the mucus glycoproteins, or mucins, are responsible for the protective gel barrier. They are characterized by their high carbohydrate content, present in their variable number, tandem repeat domains.
View Article and Find Full Text PDFIn this review, we document the evolution of common glycan structures in the eukaryotes, and illustrate the considerable variety of oligosaccharides existing in these organisms. We focus on the families of N- and O-glycans, glycosphingolipids, glycosaminoglycans, glycosylphosphatidylinositol (GPI) anchors, sialic acids (Sias), and cytoplasmic and nuclear glycans. We also outline similar and divergent aspects of the glycans during evolution within the groups, which include inter- and intraspecies differences, molecular mimicry, viral glycosylation adaptations, glycosyltransferase specificity relating to function, and the natural dynamism powering these events.
View Article and Find Full Text PDFBiochim Biophys Acta
January 2015
Background: The mucins found as components of mucus gel layers at mucosal surfaces throughout the body play roles in protection as part of the defensive barrier on an organ and tissue specific basis.
Scope Of The Review: The human MUC gene family codes up to 20 known proteins, which can be divided into secreted and membrane-associated forms each with a typical protein domain structure. The secreted mucins are adapted to cross link in order to allow formation of the extended mucin networks found in the secreted mucus gels.
Aim: The supramucosal gel, crucial for gut barrier function, might be compromised in necrotizing enterocolitis (NEC). Breast milk is associated with a reduced incidence of NEC. We compared the effects of human breast milk (BM) versus a neonatal formula, Nutriprem 1 (FF), on adherence, internalisation, and penetration of NEC-associated Escherichia coli through monolayers of mucus producing intestinal cells, HT29-MTX-E12 (E12).
View Article and Find Full Text PDFTurnover of mucins in supramucosal gels is essential for the removal of surface contaminants, and the maintenance of normal mucosal barrier function. In addition to the well-known processes promoting the physical turnover of mucus gels, extracellular mucin degradation also requires the coordinated action of a range of enzyme activities including glycosidases and proteases. These are collectively termed "mucinase".
View Article and Find Full Text PDFBackground: Mucositis is a painful ulcerative condition of the oral cavity and gastrointestinal tract, occurring in association with chemotherapy and radiotherapy regimes. Trefoil factor family peptides (TFF, trefoil peptides), present in saliva, contribute to epithelial restitution and repair and are therefore potentially important in the healing phase of mucositis. This study aimed to assess any changes in the levels of trefoil peptides in oncology patients with and without mucositis.
View Article and Find Full Text PDFIBDs (inflammatory bowel diseases) are a group of diseases affecting the gastrointestinal tract. The diseases are multifactorial and cover genetic aspects: susceptibility genes, innate and adaptive responses to inflammation, and structure and efficacy of the mucosal protective barrier. Animal models of IBD have been developed to gain further knowledge of the disease mechanisms.
View Article and Find Full Text PDFDMBT1 (deleted in malignant brain tumor 1), a human mucin-like glycoprotein, belonging to the scavenger receptor cysteine-rich (SRCR) superfamily, is mainly secreted from mucosal epithelia. It has been shown previously that interaction of hensin, the rabbit ortholog of DMBT1, with galectin 3, a β-galactoside-binding lectin, induces a terminal differentiation of epithelial cells. In this paper, we have used surface plasmon resonance (SPR), to analyse the binding of galectin 3 to two purified samples of human DMBT1:recombinant DMBT1 produced in CHO cells and DMBT1 isolated from intestinal tissues.
View Article and Find Full Text PDFBiochem Soc Trans
October 2010
The present article provides an overview on mucins and their role in biological processes, while aiming to familiarize readers with the current tools available for the synthesis of structurally defined mucin-type glycan probes including the advantages and potential applications of using ionic liquids in the synthesis of this important class of oligosaccharides. Furthermore, we also highlight recent developments in glycoarray technology that can enable high-sensitivity and high-throughput analysis of this important class of protein-carbohydrate interactions.
View Article and Find Full Text PDFThe glycans (carbohydrates) form a diverse group of biomolecules which play active parts in most physiological processes. The field of structural glycobiology concerns the structures of the glycans themselves, the proteins which interact with them and the nature of the interactions between the two. The resulting information is important for our understanding of human health and disease, and for development of new therapeutic strategies.
View Article and Find Full Text PDFThis is the first differential expression proteomics study on a human syngeneic cellular in vitro progression model of the colorectal adenoma-to-carcinoma sequence, the anchorage-dependent non-tumorigenic adenoma derived cell line AA/C1 and the derived anchorage-independent and tumorigenic carcinoma cell line AA/C1/SB10C. The study is based on quantitative 2-DE and is complemented by Western blot validation. Excluding redundancies due to proteolysis and post-translational modified isoforms of over 2000 protein spots, 13 proteins were revealed as regulated with statistical variance being within the 95th confidence level and were identified by peptide mass fingerprinting in MALDI MS.
View Article and Find Full Text PDFAtomic force microscopy (AFM) has been used to show that human ocular mucins contain at least three distinct polymer conformations, separable by isopycnic density gradient centrifugation. In this work we have used affinity purification against the anti(mucin peptide core) monoclonal antibody 45M1 to isolate MUC5AC gene products, a major component of human ocular mucins. AFM images confirm that the affinity-purified polymers adopt distinct conformations that coidentify with two of those observed in the parent population, and further reveal that these two different conformations can be present within the same polymer.
View Article and Find Full Text PDFMucin glycoproteins and trefoil peptides play an important role in protection and repair of the gastrointestinal epithelium. This study investigates alterations in mucin and trefoil peptide gene expression and product localization in ulcerative colitis (UC). Product localization and message expression of mucin MUC1 to 6 and trefoil peptide TFF1 to 3 genes was analyzed in rectosigmoid tissue from a cohort of patients with active UC and compared with that of normal colorectal mucosa.
View Article and Find Full Text PDFThe modifications to the vaginal habitat accompanying a change to vaginal flora in bacterial vaginosis (BV) are poorly understood. In this study enzymes involved in mucin degradation were measured, including a novel glycosulfatase assay. Women attending an emergency walk-in sexually transmitted disease clinic were studied.
View Article and Find Full Text PDFObjective: Airway mucins may play an important role in the mechanism of respiratory complications after cardiopulmonary bypass in infants and children. Our aim was to measure airway mucin levels before and after cardiopulmonary bypass and to determine whether changes in mucin levels were associated with the development of respiratory complications.
Methods: Airway glycoprotein and mucins (MUC5AC, MUC5B, and MUC2) in serial small-volume airway lavage samples from 39 young children who underwent cardiac operations with cardiopulmonary bypass were measured by slot-blot assay with specific antimucin peptide antibodies.
Atomic force microscopy (AFM) has been applied to the study of heterogeneity in the structure and function of individual biopolymers with complex structures such as glycoproteins, polysaccharides and nucleic acids. In this work we describe experiments which shed light on the heterogeneity of human ocular mucin gene products. By separating samples of native human ocular mucins on a caesium chloride density gradient, at least three populations consisting predominantly of products of the gene MUC5AC can be identified.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
May 2003
Purpose: Mucins are polymers that may reduce drag and enhance tear outflow. Mucin expression and distribution in human efferent tear ducts were tested in the physiological state, and potential differences in the expression pattern were investigated in the presence of primary acquired dacryostenosis (PANDO).
Methods: Expression of mucins in human lacrimal sac and nasolacrimal ducts was monitored by reverse transcription-polymerase chain reaction analysis.
Purpose: Contact lens wear alters the preocular fluid through factors that include tear deposits on the lens. In the current study, lens-adherent material was extracted to assess whether contact lenses sample mucins from the preocular fluid.
Methods: Discarded extended-wear contact lenses were collected from patients with no ocular surface disease.
Restorative proctocolectomy is regarded as a standard surgical procedure for patients who require a proctocolectomy for ulcerative colitis and familial adenomatous polyposis. The ileal mucosa undergoes colonic phenotypic change with time, but the extent and relevance of these changes to the long-term safety of the ileoanal pouch are unclear. The aim of this study was to study the mucin biology of this adaptive process in order to assess its extent and possible impact on pouch safety.
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