UGE1 and UGE2 regulate the UDP-glucose/UDP-galactose equilibrium in Cryptococcus neoformans

Frédérique Moyrand1, Thierry Fontaine2, Guilhem Janbon1

Author address: 

1Unité de Mycologie Moléculaire, Institut Pasteur, Paris, France, 2Unité des Aspergillus, Institut Pasteur, Paris, France

Abstract: 

The interactions between a pathogen and the infected host are the key to the pathogenesis of many infections. These involve different types of surfaces molecules and can be proteins, lipids or polysaccharides. However, most studies focus on proteins because they are easier to eliminate or modify through gene mutation. Polysaccharides are much more complicated to modify and their genetics, at least in eukaryotes, is far from being completely understood. However, it is obvious that, as in bacteria, their structures have a major effect on their function and on the virulence of the micro-organisms. The cell surface of the pathogenic basidiomycete yeast Cryptococcus neoformans is mainly composed of polysaccharides. The C. neoformans capsule represents a fascinating structure and we study the pathways that control its biosynthesis. It primarily comprised of two polysaccharides: glucuronoxylomannan (GXM, 88% of the capsule mass) and galactoxylomannan (GalXM, 7% of the capsule mass). Whereas most studies have focused on GXM, the genetics of the synthesis of galactomannan remained completely unknown. We have identified two paralogous genes, UGE1 and UGE2 encoding UDP-glucose/UDP-galactose epimerases. We demonstrated that UGE1 is necessary for GalXM biosynthesis and virulence whereas UGE2 is necessary for C. neoformans to grow on galactose at 30°C. Surprisingly, at 37°C, a uge28710; mutant strain grow on galactose and this grow is dependent on the presence of UGE1. We analyzed how the temperature and the sugar source influence the function of the function of this enzyme in the biology of C. neoformans
2008

abstract No: 

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Full conference title: 

9th EUROPEAN CONFERENCE ON FUNGAL GENETICS
    • ECFG 9th (2008)