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Synthesis of cell envelope glycoproteins of Cryptococcus laurentii
John Schutzbach1, Helmut Ankel, Inka Brockhausen
1Department of Medicine, Queen's University, Etherington Hall, Kingston, Ontario, Canada K7L 3N6. Inka.JSBach@kos.net
Abstract:
Fungi of the genus Cryptococcus are encapsulated basidiomycetes that are ubiquitously found in the environment. These organisms infect both lower and higher animals. Human infections that are common in immune-compromised individuals have proven difficult to cure or even control with currently available antimycotics that are quite often toxic to the host. The virulence of Cryptococcus has been linked primarily to its polysaccharide capsule, but also to cell-bound glycoproteins. In this review, we show that Cryptococcus laurentii is an excellent model for studies of polysaccharide and glycoprotein synthesis in the more pathogenic relative C. neoformans. In particular, we will discuss the structure and biosynthesis of O-linked carbohydrates on cell envelope glycoproteins of C. laurentii. These O-linked structures are synthesized by at least four mannosyltransferases, two galactosyltransferases, and at least one xylosyltransferase that have been characterized. These glycosyltransferases have no known homologues in human tissues. Therefore, enzymes involved in the synthesis of cryptococcal glycoproteins, as well as related enzymes involved in capsule synthesis, are potential targets for the development of specific inhibitors for treatment of cryptococcal disease.
Insights
Cryptococcus laurentii serves as a model for studying fungal glycoprotein synthesis. Enzymes involved in this process, like glycosyltransferases, are potential targets for new antifungal drugs.
Area of Science:
- Mycology
- Biochemistry
- Glycobiology
Background:
- Fungi of the genus Cryptococcus are environmental basidiomycetes causing infections in animals and humans.
- Cryptococcal infections are challenging to treat with existing antimycotics, which often exhibit host toxicity.
- Virulence is associated with the polysaccharide capsule and cell-bound glycoproteins.
Purpose of the Study:
- To highlight Cryptococcus laurentii as a model organism for studying fungal glycoprotein synthesis.
- To review the structure and biosynthesis of O-linked carbohydrates on C. laurentii glycoproteins.
- To identify potential therapeutic targets for cryptococcal diseases.
Main Methods:
- Review of existing literature on Cryptococcus laurentii and Cryptococcus neoformans.
- Analysis of the biosynthesis pathways for O-linked carbohydrates.
- Characterization of involved glycosyltransferases.
Main Results:
- Cryptococcus laurentii is a suitable model for studying polysaccharide and glycoprotein synthesis.
- O-linked carbohydrate structures are synthesized by specific mannosyltransferases, galactosyltransferases, and xylosyltransferases.
- These glycosyltransferases lack human homologues.
Conclusions:
- Enzymes in cryptococcal glycoprotein synthesis are potential targets for novel antifungal agents.
- Targeting these unique glycosyltransferases could lead to specific inhibitors for cryptococcal disease treatment.
- Further research into these enzymes may yield safer and more effective therapies.
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