The Candida albicans cell wall protein Rhd3/Pga29 is abundant in the yeast form and contributes to virulence.
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 beta-1,3-glucan framework of the cell wall via beta-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.
Department of Medical Microbiology and National Reference Centre for Systemic Mycoses, University Medical Centre Göttingen, Kreuzbergring 57, D-37075 Germany.
Albert D
AD
de Boer
Piet W J
PW
de Groot
Günther
G
Weindl
Martin
M
Schaller
Dietmar
D
Riedel
Rosalía
R
Diez-Orejas
Frans M
FM
Klis
Chris G
CG
de Koster
Henk L
HL
Dekker
Uwe
U
Gross
Oliver
O
Bader
Michael
M
Weig
D002176:Candida albicans / Q000737:chemistry* / Q000472:pathogenicity*; D002473:Cell Wall / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology; D005656:Fungal Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D006801:Humans; D014774:Virulence; D037521:Virulence Factors / Q000032:analysis* / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D005656:Fungal Proteins; D006023:Glycoproteins; D037521:Virulence Factors