Isolation and characterization of capsule structure mutant strains of Cryptococcus neoformans

Authors

  • Frédérique Moyrand,

    1. Unité de Mycologie Moléculaire, Institut Pasteur, 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
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  • Birgit Klaproth,

    1. Unité de Mycologie Moléculaire, Institut Pasteur, 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
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  • Uwe Himmelreich,

    1. Institute for Magnetic Resonance Research and Center for Infectious Diseases and Microbiology at Westmead Hospital, University of Sydney, Blackburn Building, NSW 2006, Australia.
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  • Françoise Dromer,

    1. Unité de Mycologie Moléculaire, Institut Pasteur, 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
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  • Guilhem Janbon

    Corresponding author
    1. Unité de Mycologie Moléculaire, Institut Pasteur, 25, rue du Dr Roux, 75724 Paris Cedex 15, France.
    • *For correspondence. E-mail janbon@pasteur.fr; Tel. (+33) 1 45 68 83 56; Fax (+33) 1 45 68 84 20

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Summary

The capsule of Cryptococcus neoformans is the most obvious virulence factor of this pathogenic yeast. The main capsule constituents are glucuronoxylomannans (GXM). Although several studies have focused on GXM composition and structure, very little is known about their genetics. To elucidate the relationship between the capsule structure and the pathophysiology of the cryptococcosis, genetic screening for mutant strains producing a structurally modified capsule was set up. Using monoclonal antibodies specific for different capsule sugar epitopes, we isolated strains with different mutated capsule structures (Cas mutants). According to their reactivities with various monoclonal antibodies, the mutants were classified into six groups (Cas1 to Cas6). One Cas2 mutant was used to clone the corresponding gene by complementation. This gene (USX1) encodes the previously identified UDP-xylose synthase. We demonstrated that it is necessary for both capsule xylosylation and C. neoformans virulence.

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