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

• Published in: Molecular microbiology Vol. 63; no. 5; pp. 1385 - 1398
• Main Authors: Reese, Amy J, Yoneda, Aki, Breger, Julia A, Beauvais, Anne, Liu, Hong, Griffith, Cara L, Bose, Indrani, Kim, Myoung-Ju, Skau, Colleen, Yang, Sarah, Sefko, Julianne A, Osumi, Masako, Latge, Jean-Paul, Mylonakis, Eleftherios, Doering, Tamara L
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.03.2007; Blackwell Publishing Ltd; Blackwell Science
• Subjects: Animals; beta-Glucans - analysis; Biochemistry; Biological and medical sciences; Caenorhabditis elegans - microbiology; Carbohydrates; Cell Wall - chemistry; Cell Wall - genetics; Cell Wall - ultrastructure; Cellular biology; Chitin - analysis; Chitosan - analysis; Cryptococcus neoformans; Cryptococcus neoformans - genetics; Cryptococcus neoformans - growth & development; Cryptococcus neoformans - pathogenicity; Cryptococcus neoformans - ultrastructure; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Fungal infections; Gene Deletion; Glucans - physiology; Glucosyltransferases - genetics; Mice; Mice, Inbred C57BL; Microbiology; Microscopy, Electron, Transmission; Miscellaneous; Mutagenesis, Insertional; Mycology; Nematoda; Plant pathology; Virulence - genetics; Fungi; Glucan; Yeast; Cryptococcus neoformans; Microbiology; Ultrastructure; Virulence; Fungi Imperfecti; Cell wall; Thallophyta
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/j.1365-2958.2006.05551.x

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.