CSDB: Search results

References to other databases: GTC:G14511SS, CCSD:33221, CBank-STR:11609
Structural formula & atomic coordinates
Sweet-II 3D model
Show glycosyltransferases

Glycosylation is an important post-translational modification that is required for structural and stability purposes and functional roles such as signalling, attachment and shielding. Many human pathogens such as bacteria display an array of carbohydrates on their surface that are non-self to the host; others such as viruses highjack the host-cell machinery and present self-carbohydrates sometimes arranged in a non-self more immunogenic manner. In combination with carrier proteins, these glycan structures can be highly immunogenic. During natural infection, glycan-binding antibodies are often elicited that correlate with long-lasting protection. A great amount of research has been invested in carbohydrate vaccine design to elicit such an immune response, which has led to the development of vaccines against the bacterial pathogens Haemophilus influenzae type b, Streptococcus pneumonia and Neisseria meningitidis. Other vaccines, e.g. against HIV-1, are still in development, but promising progress has been made with the isolation of broadly neutralizing glycan-binding antibodies and the engineering of stable trimeric envelope glycoproteins. Carbohydrate vaccines against other pathogens such as viruses (Dengue, Hepatitis C), parasites (Plasmodium) and fungi (Candida) are at different stages of development. This chapter will discuss the challenges in inducing cross-reactive carbohydrate-targeting antibodies and progress towards carbohydrate vaccines.

vaccines, immune response, Candida, glycans, Plasmodium, Dengue, Hepatitis C

NCBI PubMed ID: 30046985
Publication DOI: 10.1007/82_2018_103
Journal NLM ID: 0110513
Publisher: Heidelberg: Springer Verlag
Correspondence: Krumm SA ; Doores KJ
Institutions: Department of Infectious Diseases, King’s College London, 2nd Floor, Borough Wing, Guy’s Hospital, London, UK

Previously, we showed that Candida albicans hydrophilic yeast cells adhere specifically to mouse splenic marginal-zone macrophages. The adhesins are part of the yeast cell wall phosphomannoprotein complex, and one adhesin site, which reacts with the monoclonal antibody 10G, was identified as a β-1,2-linked tetramannose in the acid-labile portion of the complex. We report here that the acid-stable part of the complex, which has not been reported previously to have adhesin activity, is in large part responsible for yeast cell binding to the splenic marginal zone. The phosphomannoprotein complex, termed Fr.II, was isolated from C. albicans serotype B yeast cells by β-mercaptoethanol extraction and concanavalin A-agarose affinity chromatography. Fr.II is devoid of the serotype A-specific antigen factor 6, which functions in yeast cell attachment to epithelial cells. The acid-stable part of Fr.II (i.e., Fr.IIS) was obtained by mild acid hydrolysis and size exclusion fractionation. Fr.IIS was further fractionated into four fractions, Fr.IIS1, Fr.IIS2, Fr.IIS3, and Fr.IIS4, by concanavalin A-agarose column chromatography and elution with a linear gradient of α-methyl-D-mannopyranoside. Adhesin activity of these fractions was determined by their ability to block yeast cell binding to the splenic marginal zone. Fr.IIS1 and Fr.IIS2 yielded more material and stronger adhesin activity than either Fr.IIS3 or Fr.IIS4. Only Fr.IIS1 did not react with antibodies (anti-factor 5 and monoclonal antibody 10G) specific for the acid-labile β-1,2-linked oligosaccharides. Fr.IIS1-coated latex beads attached specifically to the marginal zone in a pattern identical to that of yeast cell binding. Furthermore, Fr.IIS1-latex bead attachment was inhibited by soluble Fr.II or Fr.IIS. Initial chemical analyses indicate that the adhesin site on Fr.IIS1 is a carbohydrate because adhesin activity was destroyed by periodate oxidation but not by proteinase K digestion.

NCBI PubMed ID: 8168927
Journal NLM ID: 0246127
Publisher: American Society for Microbiology
Institutions: Laboratory of Medical Mycology, Nagoya University School of Medicine, Japan

An antigen (Ag), as defined by reactivity with a monoclonal antibody (mAb 10G), was found on the cell wall surface and on the plasma membrane of Candida albicans yeast cells (Li, R. K., and Cutler, J. E. (1991) J. Gen. Microbiol. 137, 455-464). The 10G Ag from the cell surface location was solubilized by treatment with β-mercaptoethanol and Zymolyase. Antigenic activity of the extract was lost following periodate oxidation, but was stable to proteolytic enzyme and heat treatments. Mannoproteins in the extract were fractionated by hexadecyltrimethylammonium bromide. A fraction containing the 10G Ag was degraded by mild acid hydrolysis and a tetrahexose eluted from a P-2 size exclusion column was found to be the epitope (10G epitope) part of the 10G Ag. By use of gas-liquid chromatography, mass spectroscopy, and H-1 proton NMR analysis, the 10G epitope was determined to be a linear β-1,2-linked tetramannose. The 10G Ag, which was immunopurified from the Zymolyase extract, and the 10G epitope were involved in the attachment of C. albicans to mouse spleen marginal zone macrophages. Both the 10G Ag and the purified 10G epitope specifically inhibited C. albicans adherence in an ex vivo binding assay. Latex beads adsorbed with the 10G Ag or the 10G epitope adhered specifically to the splenic marginal zone macrophages. These data show that a β-1,2-linked mannotetraose part of a C. albicans cell wall mannoprotein is an adhesin site that may play a role in pathogenesis of disseminated candidiasis.

NCBI PubMed ID: 7688744
Journal NLM ID: 2985121R
Publisher: Baltimore, MD: American Society for Biochemistry and Molecular Biology
Institutions: Department of Microbiology, Montana State University, Bozeman 59717
Methods: 1H NMR, GC-MS