title: Unusual galactofuranose modification of a capsule polysaccharide in the pathogenic yeast Cryptococcus neoformans.
abstract: Galactofuranose (Galf) is the five-membered ring form of galactose. Although it is absent from mammalian glycans, it occurs as a structural and antigenic component of important cell surface molecules in a variety of microbes, ranging from bacteria to parasites and fungi. One such organism is Cryptococcus neoformans, a pathogenic yeast that causes lethal meningoencephalitis in immunocompromised individuals, particularly AIDS patients. C. neoformans is unique among fungal pathogens in bearing a complex polysaccharide capsule, a critical virulence factor reported to include Galf. Notably, how Galf modification contributes to the structure and function of the cryptococcal capsule is not known. We have determined that Galf is β1,2-linked to an unusual tetrasubstituted galactopyranose of the glucuronoxylomannogalactan (GXMGal) capsule polysaccharide. This discovery fills a longstanding gap in our understanding of a major polymer of the cryptococcal capsule. We also engineered a C. neoformans strain that lacks UDP-galactopyranose mutase; this enzyme forms UDP-Galf, the nucleotide sugar donor required for Galf addition. Mutase activity was required for the incorporation of Galf into glucuronoxylomannogalactan but was dispensable for vegetative growth, cell integrity, and virulence in a mouse model.
authors: Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA.
authors: Christian
authors: C
authors: Heiss
authors: Michael L
authors: ML
authors: Skowyra
authors: Hong
authors: H
authors: Liu
authors: J Stacey
authors: JS
authors: Klutts
authors: Zhirui
authors: Z
authors: Wang
authors: Matthew
authors: M
authors: Williams
authors: Deepa
authors: D
authors: Srikanta
authors: Stephen M
authors: SM
authors: Beverley
authors: Parastoo
authors: P
authors: Azadi
authors: Tamara L
authors: TL
authors: Doering
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003455:Cryptococcus neoformans / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D004195:Disease Models, Animal; D062607:Fungal Capsules / Q000235:genetics / Q000378:metabolism*; D062610:Fungal Polysaccharides / Q000235:genetics / Q000378:metabolism*; D005690:Galactose / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000235:genetics / Q000378:metabolism; D051379:Mice
chemical_list: D062610:Fungal Polysaccharides; D005690:Galactose