Complete glycosylphosphatidylinositol anchors are required in Candida albicans for full morphogenesis, virulence and resistance to macrophages.

Abstract

Glycosylphosphatidylinositol (GPI)-anchored proteins are involved in cell wall integrity and cell-cell interactions. We disrupted the Candida albicans homologue of the Saccharomyces cerevisiae GPI7/LAS21 gene, which encodes a GPI anchor-modifying activity. In the mutant and on solid media, the yeast-to-hyphae transition was blocked, whereas chlamydospore formation was enhanced. However, the morphogenetic switch was normal in liquid medium. Abnormal budding patterns, cytokinesis and cell shape were observed in both liquid and solid media. The cell wall structure was also modified in the mutants, as shown by hypersensitivity to Calcofluor white. In vitro and in vivo assays revealed that the mutant interacted with its host in a modified way, resulting in reduced virulence in mice and reduced survival in the gastrointestinal environment of mice. The mitogen-activated protein (MAP) kinase pathway of macrophages was downregulated by the wild-type cells but not by the DeltaCagpi7 null strains. In agreement with this abnormal behaviour, mutant cells were more sensitive to the lytic action of macrophages. Our results indicate that a functional GPI anchor is required for full hyphal formation in C. albicans, and that perturbation of the GPI biosynthesis results in hypersensitivity to host defences.

• Authors: Mathias Richard, Stella Ibata-Ombetta, Françoise Dromer, Florence Bordon-Pallier, Thierry Jouault, Claude Gaillardin
• Journal: Molecular microbiology (Mol Microbiol) Vol. 44 Issue 3 Pg. 841-53 (May 2002) ISSN: 0950-382X [Print] England
• PMID: 11994163 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antifungal Agents
• Benzenesulfonates
• Fungal Proteins
• Glycosylphosphatidylinositols
• Saccharomyces cerevisiae Proteins
• C.I. Fluorescent Brightening Agent 28
• LAS21 protein, S cerevisiae
• Phosphotransferases (Alcohol Group Acceptor)
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Antifungal Agents (pharmacology)
• Benzenesulfonates (pharmacology)
• Candida albicans (drug effects, metabolism, pathogenicity, ultrastructure)
• Candidiasis (microbiology)
• Cell Wall (chemistry, metabolism)
• Digestive System (microbiology)
• Drug Resistance, Fungal
• Fungal Proteins (genetics, metabolism)
• Fungemia (microbiology)
• Glycosylphosphatidylinositols (metabolism)
• Hot Temperature
• MAP Kinase Signaling System
• Macrophages (physiology)
• Mice
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases (metabolism)
• Morphogenesis
• Phagocytosis
• Phosphorylation
• Phosphotransferases (Alcohol Group Acceptor) (genetics, metabolism)
• Protein Processing, Post-Translational
• Saccharomyces cerevisiae Proteins
• Spores, Fungal
• Virulence