CSDB: Search results

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

NCBI PubMed ID: 18588334
Publication DOI: 10.1021/jp8018205
Journal NLM ID: 101157530
Publisher: 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
Methods: immunofluorescence analyses, confocal scanning laser microscopy