Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence

Détails

ID Serval
serval:BIB_34F59B00720E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence
Périodique
Infection and Immunity
Auteur(s)
Hube  B., Sanglard  D., Odds  F. C., Hess  D., Monod  M., Schafer  W., Brown  A. J., Gow  N. A.
ISSN
0019-9567 (Print)
Statut éditorial
Publié
Date de publication
09/1997
Volume
65
Numéro
9
Pages
3529-38
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep
Résumé
Secreted aspartyl proteinases (Saps), encoded by a gene family with at least nine members (SAP1 to SAP9), are one of the most discussed virulence factors produced by the human pathogen Candida albicans. In order to study the role of each Sap isoenzyme in pathogenicity, we have constructed strains which harbor mutations at selected SAP genes. SAP1, SAP2, and SAP3, which are regulated differentially in vitro, were mutated by targeted gene disruption. The growth rates of all homozygous null mutants were similar to those of the isogenic wild-type parental strain (SC5314) in complex and defined media. In medium with protein as the sole source of nitrogen, sap1 and sap3 mutants grew with reduced growth rates but reached optical densities similar to those measured for SC5314. In contrast, sap2 null mutants tended to clump, grew poorly in this medium, and produced the lowest proteolytic activity. Addition of ammonium ions reversed such growth defects. These results support the view that Sap2 is the dominant isoenzyme. When sap1, sap2, and sap3 mutants were injected intravenously in guinea pigs and mice, the animals had increased survival rates compared to those of control animals infected with SC5314. However, reduction of proteolytic activity in vitro did not correlate directly with the extent of attenuation of virulence observed for all Sap-deficient mutants. These data suggest that SAP1, SAP2, and SAP3 all contribute to the overall virulence of C. albicans and presumably all play important roles during disseminated infections.
Mots-clé
Animals Aspartic Endopeptidases/*genetics/metabolism/secretion Candida albicans/enzymology/genetics/*pathogenicity Candidiasis/microbiology Genes, Fungal Guinea Pigs Mice Mutagenesis, Insertional Vaccines, Attenuated
Pubmed
Web of science
Création de la notice
25/01/2008 17:47
Dernière modification de la notice
20/08/2019 14:22
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