Evidence for branching in cryptococcal capsular polysaccharides and consequences on its biological activity
Open Access
- 5 January 2011
- journal article
- Published by Wiley in Molecular Microbiology
- Vol. 79 (4), 1101-1117
- https://doi.org/10.1111/j.1365-2958.2010.07511.x
Abstract
The encapsulated fungus Cryptococcus neoformans is a common cause of life‐threatening disease in immunocompromised individuals. Its major virulence determinant is the polysaccharide (PS) capsule. An unsolved problem in cryptococcal biology is whether the PSs composing the capsule are linear or complex branched polymers, as well as the implications of this structural composition in pathogenesis. In this study we approached the problem by combining static and dynamic light scattering, viscosity analysis, and high‐resolution microscopy and correlated the findings with biological properties. Analysis of the dependence of capsular PS molecular mass and the radius of gyration provided strong evidence against a simple linear PS configuration. Shape factors calculated from light scattering measurements in solution revealed values consistent with polymer branching. Furthermore, viscosity measurements provided complementary evidence for structural branching. Electron microscopy showed PS spherical‐like structures similar to other branched PS. Finally, we show that the capacity of capsular PS to interfere in complement‐mediated phagocytosis, inhibit nitric oxide production by macrophage‐like cells, protect against reactive oxygen species, antibody reactivity and half‐life in serum were influenced by the degree of branching, providing evidence for the notion that PS branching is an important parameter in determining the biological activity of C. neoformans PS.Keywords
This publication has 79 references indexed in Scilit:
- Cryptococcus neoformans responds to mannitol by increasing capsule size in vitro and in vivoCellular Microbiology, 2010
- Vesicle-associated melanization in Cryptococcus neoformansMicrobiology, 2009
- Role for Chitin and Chitooligomers in the Capsular Architecture of Cryptococcus neoformansEukaryotic Cell, 2009
- Production of Extracellular Polysaccharides by CAP Mutants of Cryptococcus neoformansEukaryotic Cell, 2009
- Chapter 4 The Capsule of the Fungal Pathogen Cryptococcus neoformansAdvances in Applied Microbiology, 2009
- Capsule ofCryptococcus neoformansgrows by enlargement of polysaccharide moleculesProceedings of the National Academy of Sciences of the United States of America, 2009
- Capsule Structural Heterogeneity and Antigenic Variation in Cryptococcus neoformansEukaryotic Cell, 2007
- Self-Aggregation of Cryptococcus neoformans Capsular Glucuronoxylomannan Is Dependent on Divalent CationsEukaryotic Cell, 2007
- Loss of cell wall alpha(1‐3) glucan affects Cryptococcus neoformans from ultrastructure to virulenceMolecular Microbiology, 2006
- A Eukaryotic Capsular Polysaccharide Is Synthesized Intracellularly and Secreted via ExocytosisMolecular Biology of the Cell, 2006