Unusual Galactofuranose Modification of a Capsule Polysaccharide in the Pathogenic Yeast Cryptococcus neoformans

Christian Heiss; Michael L Skowyra; Hong Liu; J.Stacey Klutts; Zhirui Wang; Matthew Williams; Deepa Srikanta; Stephen M Beverley; Parastoo Azadi; Tamara L Doering

doi:10.1074/jbc.M112.441998

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Unusual Galactofuranose Modification of a Capsule Polysaccharide in the Pathogenic Yeast Cryptococcus neoformans

Journal article

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Unusual Galactofuranose Modification of a Capsule Polysaccharide in the Pathogenic Yeast Cryptococcus neoformans

Christian Heiss, Michael L Skowyra, Hong Liu, J.Stacey Klutts, Zhirui Wang, Matthew Williams, Deepa Srikanta, Stephen M Beverley, Parastoo Azadi and Tamara L Doering

The Journal of biological chemistry, Vol.288(16), pp.10994-11003

04/19/2013

DOI: 10.1074/jbc.M112.441998

PMCID: PMC3630864

PMID: 23408430

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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. Background: Galactofuranose, the five-membered ring form of galactose, occurs in the encapsulated pathogenic fungus Cryptococcus neoformans but not in humans. Results: We established the position of galactofuranose within a capsule polysaccharide and characterized cryptococci lacking this modification. Conclusion: Galactofuranose occurs in an unusual linkage but is not required for growth or virulence. Significance: This work fills a gap in knowledge about a pathogen-specific modification.

Capsule

Carbohydrate Structure

Cryptococcus neoformans

Fungi

Galactofuranose

GalXM

GXMGal

Microbial Pathogenesis

Microbiology

NMR

Details

Title: Subtitle: Unusual Galactofuranose Modification of a Capsule Polysaccharide in the Pathogenic Yeast Cryptococcus neoformans
Creators: Christian Heiss - University of Georgia
Michael L Skowyra - Washington University in St. Louis
Hong Liu - Washington University in St. Louis
J.Stacey Klutts - Washington University in St. Louis
Zhirui Wang - University of Georgia
Matthew Williams - Washington University in St. Louis
Deepa Srikanta - Washington University in St. Louis
Stephen M Beverley - Washington University in St. Louis
Parastoo Azadi - University of Georgia
Tamara L Doering - Washington University in St. Louis
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.288(16), pp.10994-11003
DOI: 10.1074/jbc.M112.441998
PMID: 23408430
PMCID: PMC3630864
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Language: English
Date published: 04/19/2013
Academic Unit: Pathology
Record Identifier: 9984186544802771

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