The CRH family coding for cell wall glycosylphosphatidylinositol proteins with a predicted transglycosidase domain affects cell wall organization and virulence of Candida albicans.

Détails

ID Serval
serval:BIB_A411FA969957
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The CRH family coding for cell wall glycosylphosphatidylinositol proteins with a predicted transglycosidase domain affects cell wall organization and virulence of Candida albicans.
Périodique
Journal of Biological Chemistry
Auteur(s)
Pardini G., De Groot P.W., Coste A.T., Karababa M., Klis F.M., de Koster C.G., Sanglard D.
ISSN
0021-9258
Statut éditorial
Publié
Date de publication
12/2006
Peer-reviewed
Oui
Volume
281
Numéro
52
Pages
40399-40411
Langue
anglais
Notes
Publication types: Journal Article
Résumé
In Candida albicans UTR2 (CSF4), CRH11, and CRH12 are members of a gene family (the CRH family) that encode glycosylphosphatidylinositol-dependent cell wall proteins with putative transglycosidase activity. Deletion of genes of this family resulted in additive sensitivity to compounds interfering with normal cell wall formation (Congo red, calcofluor white, SDS, and high Ca(2+) concentrations), suggesting that these genes contribute to cell wall organization. A triple mutant lacking UTR2, CRH11, and CRH12 produced a defective cell wall, as inferred from increased sensitivity to cell wall-degrading enzymes, decreased ability of protoplasts to regenerate a new wall, constitutive activation of Mkc1p, the mitogen-activated protein kinase of the cell wall integrity pathway, and an increased chitin content of the cell wall. Importantly, this was accompanied by a decrease in alkali-insoluble 1,3-beta-glucan but not total glucan content, suggesting that formation of the linkage between 1,3-beta-glucan and chitin might be affected. In support of this idea, localization of a Utr2p-GFP fusion protein largely coincided with areas of chitin incorporation in C. albicans.As UTR2 and CRH11 expression is regulated by calcineurin, a serine/threonine protein phosphatase involved in tolerance to antifungal drugs, cell wall morphogenesis, and virulence, this points to a possible relationship between calcineurin and the CRH family. Deletion of UTR2, CRH11, and CRH12 resulted in only a partial overlap with calcineurin-dependent phenotypes, suggesting that calcineurin has additional targets. Interestingly, cells deleted for UTR2, CRH11, and CRH12 were, like a calcineurin mutant, avirulent in a mouse model of systemic infection but retained the capacity to colonize target organs (kidneys) as the wild type. In conclusion, this work establishes the role of UTR2, CRH11, and CRH12 in cell wall organization and integrity.
Mots-clé
Animals, Candida albicans/enzymology, Candida albicans/genetics, Candidiasis/enzymology, Candidiasis/metabolism, Cell Wall/enzymology, Cell Wall/genetics, Congo Red/chemistry, Fungal Proteins/chemistry, Fungal Proteins/genetics, Gene Deletion, Glycoside Hydrolases/chemistry, Glycoside Hydrolases/genetics, Glycosylphosphatidylinositols/chemistry, Glycosylphosphatidylinositols/physiology, Mice, Multienzyme Complexes/chemistry, Multienzyme Complexes/physiology, Multigene Family, Protein Structure, Tertiary, Transferases/chemistry, Transferases/physiology, Virulence Factors/chemistry, Virulence Factors/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 15:40
Dernière modification de la notice
20/08/2019 16:09
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