Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
Organ / tissue: capsuleAssociated disease: infection due to Cryptococcus neoformans [ICD11:
XN3EH 
]
NCBI PubMed ID: 18588334Publication DOI: 10.1021/jp8018205Journal NLM ID: 101157530Publisher: Washington, DC: American Chemical Society
Institutions: Department of Biological and Environmental Engineering, Cornell University, Ithaca, USA, Department of Nuclear Medicine, Albert Einstein College of Medicine, New York, NY, USA, Howard Hughes Medical Institute - Medical Fellows Program, Chevy Chase, USA, The Mount Sinai School of Medicine, New York, USA, Mycology Unit, National Center for Microbiology. Instituto de Salud Carlos III, Madrid, Spain, Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA, Medicine, Albert Einstein College of Medicine, New York, NY, USA
Many microorganisms such as bacteria and fungi possess so-called capsules made of polysaccharides which protect these microorganisms from environmental insults and host immune defenses. The polysaccharide capsule of Cryptococcus neoformans, a human pathogenic yeast, is capable of self-assembly, composed mostly of glucuronoxylomannan (GXM), a polysaccharide with a molecular weight of approximately 2000000, and has several layers with different densities. The objective of this study was to model pore-hindered diffusion and binding of the GXM-specific antibody within the C. neoformans capsule. Using the finite-element method (FEM), we created a model which represents the in vivo binding of a GXM-specific antibody to a C. neoformans cell taking into account the intravenous infusion time of antibody, antibody diffusion through capsular pores, and Michaelis-Menten kinetics of antibody binding to capsular GXM. The model predicted rapid diffusion of antibody to all regions of the capsule where the pore size was greater than the Stokes diameter of the antibody. Binding occurred primarily at intermediate regions of the capsule. The GXM concentration in each capsular region was the principal determinant of the steady-state antibody-GXM complex concentration, while the forward binding rate constant influenced the rate of complex formation in each region. The concentration profiles predicted by the model closely matched experimental immunofluorescence data. Inclusion of different antibody isotypes (IgG, IgA, and IgM) into the modeling algorithm resulted in similar complex formation in the outer capsular regions, but different depths of binding at the inner regions. These results have implications for the development of new antibody-based therapies
Glucuronoxylomannan, Cryptococcus neoformans capsule, mathematical model, finite element method, Michaelis-Menten kinetics, pore-hindered diffusion
Structure type: suggested polymer biological repeating unit
Location inside paper: Fig. 1, b
Trivial name: glucuronoxylomannan (GXM)
Compound class: CPS, EPS, O-polysaccharide, O-antigen, cell wall polysaccharide, polysaccharide, glucuronoxylomannan, capsule polysaccharide
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_130701,IEDB_140116,IEDB_140630,IEDB_144983,IEDB_145668,IEDB_152206,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72
Methods: immunofluorescence analyses, confocal scanning laser microscopy
Related record ID(s): 49260, 49262
NCBI Taxonomy refs (TaxIDs): 235443Reference(s) to other database(s): GTC:G53406VG
Show glycosyltransferases
There is only one chemically distinct structure:
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(later renamed to: Cryptococcus neoformans var. grubii H99)