Loss of cell wall alpha(1-3) glucan affects Cryptococcus neoformans from ultrastructure to virulence

Amy J. Reese, Aki Yoneda, Julia A. Breger, Anne Beauvais, Hong Liu, Cara L. Griffith, Indrani Bose, Myoung Ju Kim, Colleen Skau, Sarah Yang, Julianne A. Sefko, Masako Osumi, Jean Paul Latge, Eleftherios Mylonakis, Tamara L. Doering

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

Yeast cell walls are critical for maintaining cell integrity, particularly in the face of challenges such as growth in mammalian hosts. The pathogenic fungus Cryptococcus neoformans additionally anchors its polysaccharide capsule to the cell surface via α(1-3) glucan in the wall. Cryptococcal cells disrupted in their alpha glucan synthase gene were sensitive to stresses, including temperature, and showed difficulty dividing. These cells lacked surface capsule, although they continued to shed capsule material into the environment. Electron microscopy showed that the alpha glucan that is usually localized to the outer portion of the cell wall was absent, the outer region of the wall was highly disorganized, and the inner region was hypertrophic. Analysis of cell wall composition demonstrated complete loss of alpha glucan accompanied by a compensatory increase in chitin/chitosan and a redistribution of beta glucan between cell wall fractions. The mutants were unable to grow in a mouse model of infection, but caused death in nematodes. These studies integrate morphological and biochemical investigations of the role of alpha glucan in the cryptococcal cell wall.

Original languageEnglish (US)
Pages (from-to)1385-1398
Number of pages14
JournalMolecular Microbiology
Volume63
Issue number5
DOIs
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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