Inositol acylation of glycosylphosphatidylinositols in the pathogenic fungus Cryptococcus neoformans and the model yeast Saccharomyces cerevisiae

Sarah P. Franzot, Tamara L. Doering

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Cryptococcus neoformans, an opportunistic fungus responsible for life-threatening infection in immunocompromised patients, is able to synthesize glycosylphosphatidylinositol (GPI) structures. Radiolabelling experiments in vitro with the use of a cryptococcal cell-free system showed that the pathway begins as in other eukaryotes, with the addition of N-acetylglucosamine to phosphatidylinositol, followed by deacetylation of the sugar residue. The third step, acylation of the inositol ring, seemed to involve a fatty acid other than palmitate, in contrast with previous findings in Saccharomyces cerevisiae and mammalian GPI pathways. A systematic study of inositol acylation in C. neoformans and S. cerevisiae showed that both organisms used a variety of fatty acids in this step; these were transferred directly from acyl-CoA to inositol without modification. However, the specificity of fatty acid utilization was quite distinct in the two fungi, with the pathogen being substantially more restrictive. In mammalian cells fatty acids added exogenously as acyl-CoAs are not transferred directly to inositol. These results suggest significant differences in the GPI biosynthetic pathway between mammalian and C. neoformans cells that could represent targets for anti-cryptococcal therapy.

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalBiochemical Journal
Volume340
Issue number1
DOIs
StatePublished - May 15 1999
Externally publishedYes

Keywords

  • Cryptococcal and mammalian glycosylphosphatidylinositols (GPIs)
  • Fatty acids
  • GPI anchors
  • GPI biosynthesis

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