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A more recent version of this article appeared on January 27, 2006
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M509465200v1
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Papers In Press, published online ahead of print November 8, 2005
J. Biol. Chem, 10.1074/jbc.M509465200
Submitted on August 26, 2005
Revised on November 3, 2005
Accepted on November 8, 2005

The physical properties of the capsular polysaccharides from cryptococcus neoformans suggest features for capsule construction

Diane C. McFadden, Magdia De Jesus, and Arturo Casadevall

Department of Medicine, Division of Infectious Disease, Albert Einstein College of Medicine, Bronx, NY 10461

Corresponding Author: casadeva{at}aecom.yu.edu

The most distinctive feature of the human pathogenic fungus is a polysaccharide capsule that is essential for virulence and is composed primarily of glucuronoxylomannan (GXM) and galactoxylomannan (GalXM). GXM mediates multiple deleterious effects on host immune function yet relatively little is known about its physical properties. The average mass of C. neoformans GXM from four antigenically different strains ranged from 1.7-7 x 106 daltons as calculated from Zimm plots of light scattering data. GalXM was significantly smaller than GXM with an average mass of 1 x 105 daltons. These molecular weights imply that GalXM is the most numerous polysaccharide in the capsule on a molar basis. The radius of gyration of the capsular polysaccharides ranged between 68 and 208 nm. Viscosity measurements suggest that neither polysaccharide altered fluid dynamics during infection since GXM behaved in solution as a polyelectrolyte and GalXM did not increase solution viscosity. Immunoblot analysis indicated heterogeneity within GXM. In agreement with this, scanning transmission electron microscopy (STEM) of GXM preparations revealed a tangled network of two different types of molecules. Mass per length measurements from light scattering and STEM were consistent and suggested GXM molecules self-associate. A mechanism for capsule construction is proposed based on the extracellular release and entanglement of GXM molecules


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