Candida albicans secreted aspartic proteases 4-6 induce apoptosis of epithelial cells by a novel Trojan horse mechanism.

Détails

ID Serval
serval:BIB_12C4E50F1615
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Candida albicans secreted aspartic proteases 4-6 induce apoptosis of epithelial cells by a novel Trojan horse mechanism.
Périodique
FASEB Journal
Auteur⸱e⸱s
Wu H., Downs D., Ghosh K., Ghosh A.K., Staib P., Monod M., Tang J.
ISSN
1530-6860 (Electronic)
ISSN-L
0892-6638
Statut éditorial
Publié
Date de publication
2013
Volume
27
Numéro
6
Pages
2132-2144
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish. PDF type: Research Communication
Résumé
Systemic infection by the pathogenic yeast Candida albicans produces high mortality in immune-compromised people. Such infection starts with the penetration of the organism at the mucosal surfaces, facilitated by the secreted aspartic proteases (Saps) 4, 5, and 6. The functional mechanism of these virulence factors is unclear. We discovered that Saps 4-6 each contains amino acid motifs RGD/KGD to bind integrins on epithelial cell A549 and are internalized to endosomes and lysosomes. These processes are inhibited by RGD-containing peptides or by substituting RGD motifs of these Saps. The internalization of Saps 4-6 results in partial permeabilization of lysosomal membranes, measured by the redistribution of the lysosomal tropic dye acridine orange to the cytosol, and the triggering of apoptosis via caspase activation. Sap 2 and mutated Saps 4-6 contain no RGD motif, are ineffective in these processes, and a proteolytic inhibitor abolished Sap 4 activity in lysosome permeabilization. Same results were also seen for human tongue keratinocyte SCC-15 cells. Mucosal lesions from this fundamental new mechanism may permit C. albicans to enter the body and may be used to attack cells in immune defense during systemic infections. RGD-motif may also be incorporated in Sap inhibitors for Candidiasis drugs targeting to lysosomes.-Wu, H., Downs, D., Ghosh, K., Ghosh, A. K., Staib, P., Monod, M., and Tang, J. Candida albicans secreted aspartic proteases 4-6 induce apoptosis of epithelial cells by a novel Trojan horse mechanism.
Pubmed
Web of science
Création de la notice
04/07/2013 19:44
Dernière modification de la notice
20/08/2019 12:41
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