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Evidence for branching in cryptococcal capsular polysaccharides and consequences on its biological activity
Author(s) -
Cordero Radames J. B.,
Frases Susana,
Guimaräes Allan J.,
Rivera Johanna,
Casadevall Arturo
Publication year - 2011
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2010.07511.x
Subject(s) - branching (polymer chemistry) , radius of gyration , biology , cryptococcus neoformans , biophysics , polysaccharide , complement system , microbiology and biotechnology , polymer , biochemistry , materials science , immunology , antibody , composite material
Summary 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.