Evidence for branching in cryptococcal capsular polysaccharides and consequences on its biological activity

Radames J B Cordero, Susana Frases, Allan J. Guimaräes, Johanna Rivera, Arturo Casadevall

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1101-1117
Number of pages17
JournalMolecular Microbiology
Volume79
Issue number4
DOIs
StatePublished - Feb 2011

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Polysaccharides
Cryptococcus neoformans
Viscosity
Capsules
Polymers
cryptococcal polysaccharide
Phagocytosis
Half-Life
Virulence
Microscopy
Reactive Oxygen Species
Electron Microscopy
Nitric Oxide
Fungi
Macrophages
Light
Antibodies
Serum

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

Evidence for branching in cryptococcal capsular polysaccharides and consequences on its biological activity. / Cordero, Radames J B; Frases, Susana; Guimaräes, Allan J.; Rivera, Johanna; Casadevall, Arturo.

In: Molecular Microbiology, Vol. 79, No. 4, 02.2011, p. 1101-1117.

Research output: Contribution to journalArticle

Cordero, Radames J B ; Frases, Susana ; Guimaräes, Allan J. ; Rivera, Johanna ; Casadevall, Arturo. / Evidence for branching in cryptococcal capsular polysaccharides and consequences on its biological activity. In: Molecular Microbiology. 2011 ; Vol. 79, No. 4. pp. 1101-1117.
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