Candida albicans cell wall protein Rhd3/Pga29 is abundant in the yeast form and contributes to virulence

• Published in: Yeast (Chichester, England) England), 2010-08, Vol.27 (8), p.611-624
• Main Authors: de Boer, Albert D, de Groot, Piet W.J, Weindl, Günther, Schaller, Martin, Riedel, Dietmar, Diez-Orejas, Rosalía, Klis, Frans M, de Koster, Chris G, Dekker, Henk L, Gross, Uwe, Bader, Oliver, Weig, Michael
• Format: Article
• Language: English
• Subjects: Candida albicans; Candida albicans - chemistry; Candida albicans - pathogenicity; Cell Wall - chemistry; cell wall protein; cytokines; Cytokines - secretion; Epithelial Cells - microbiology; Fungal Proteins - analysis; Fungal Proteins - genetics; Fungal Proteins - physiology; Gene Deletion; Glycoproteins - analysis; Glycoproteins - genetics; Glycoproteins - physiology; host‐pathogen interactions; Humans; mannan; O‐glycosylation; proteomics; Virulence; Virulence Factors - analysis; Virulence Factors - genetics; Virulence Factors - physiology
• ISSN: 0749-503X; 1097-0061; 1097-0061
• DOI: 10.1002/yea.1790

The glycosylphosphatidylinositol-modified protein Rhd3/Pga29 of the human pathogen Candida albicans belongs to a family of cell wall proteins that are widespread among Candida species but are not found in other fungi. Pga29 is covalently linked to the β-1,3-glucan framework of the cell wall via β-1,6-glucan. It is a small and abundant O-glycosylated protein and requires the protein-O-mannosyl transferase Pmt1 for glycosylation. Furthermore, Pga29 is strongly expressed in yeast cells but is downregulated in hyphae. Removal of the PGA29 gene in C. albicans leads to a significant reduction of cell wall mannan; however, Pga29 does not seem to have a major role in maintaining cell wall integrity. In addition, adhesion capacity and hyphae formation appear normal in pga29 deletion mutants. Importantly, the pga29 deletion mutant is less virulent, and infection of reconstituted human epithelium with the pga29 mutant results in a diminished induction of proinflammatory cytokines, such as GM-CSF, TNF, IL-6 and IL-8. We propose that the reduced virulence of the pga29 mutant is a consequence of altered surface properties, resulting in altered fungal recognition. Copyright © 2010 John Wiley & Sons, Ltd.