ArticleAntimicrobial agents and chemotherapy2008
Tetracycline-inducible expression of individual secreted aspartic proteases in Candida albicans allows isoenzyme-specific inhibitor screening.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Article
- A highly conserved tRNA modification contributes toMicrobiology spectrum · 2024Article
- Secreted Aspartic Proteinases: Key Factors inInternational journal of molecular sciences · 2024Review
- 2,4-Diacetylphloroglucinol ModulatesJournal of fungi (Basel, Switzerland) · 2022Article
- The Role of B-Cells and Antibodies againstVaccines · 2021Review
- The histone chaperone HIR maintains chromatin states to control nitrogen assimilation and fungal virulence.Cell reports · 2021Article
- Vaccination with Secreted Aspartyl Proteinase 2 Protein fromInfection and immunity · 2020Article
- Investigating Common Pathogenic Mechanisms betweenToxins · 2019Article
- Propeptide genesis by Kex2-dependent cleavage of yeast wall protein 1 (Ywp1) of Candida albicans.PloS one · 2018Article
- Article
- Csr1/Zap1 Maintains Zinc Homeostasis and Influences Virulence in Candida dubliniensis but Is Not Coupled to Morphogenesis.Eukaryotic cell · 2015Article
- Candida albicans OPI1 regulates filamentous growth and virulence in vaginal infections, but not inositol biosynthesis.PloS one · 2015Article
- Candida albicans secreted aspartic proteases 4-6 induce apoptosis of epithelial cells by a novel Trojan horse mechanism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Article
- Factors supporting cysteine tolerance and sulfite production in Candida albicans.Eukaryotic cell · 2013Article
- Rhb1 regulates the expression of secreted aspartic protease 2 through the TOR signaling pathway in Candida albicans.Eukaryotic cell · 2012Article
- Loss of heterozygosity at an unlinked genomic locus is responsible for the phenotype of a Candida albicans sap4Δ sap5Δ sap6Δ mutant.Eukaryotic cell · 2011Article
- Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans.PloS one · 2011Article
- The glycosylphosphatidylinositol-anchored protease Sap9 modulates the interaction of Candida albicans with human neutrophils.Infection and immunity · 2009Article
- Oral candidiasis in HIV-uninfected pediatric population in areas with limited fungal diagnosis: A case study from a tertiary hospital, Tanzania.Therapeutic advances in infectious diseaseArticle
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8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The yeast Candida albicans possesses a gene family that encodes secreted aspartic proteases (Saps), which are important for the virulence of this human fungal pathogen. Inhibitors of the Saps could therefore be used as novel antimycotic agents for the treatment of C. albicans infections. In the present study, we established a bioassay which allows testing of the activity of potential protease inhibitors against specific Sap isoenzymes by their ability to inhibit protease-dependent growth of C. albicans. In a medium containing bovine serum albumin (BSA) as the sole source of nitrogen, C. albicans specifically expresses the Sap2p isoenzyme, which degrades the BSA and thereby enables the fungus to grow. As the other SAP genes are not significantly expressed under these conditions, mutants lacking SAP2 are unable to utilize BSA as a nitrogen source and cannot grow in such a medium. To investigate whether forced expression of SAP genes other than SAP2 would also allow growth on BSA, we constructed a set of strains expressing each of the 10 SAP genes from a tetracycline-inducible promoter in a sap2Delta mutant background. Expression of Sap1p, Sap2p, Sap3p, Sap4p, Sap5p, Sap6p, Sap8p, and a C-terminally truncated, secreted Sap9p restored the growth of the sap2Delta mutant with different efficiencies. This set of strains was then used to test the activities of various aspartic protease inhibitors against specific Sap isoenzymes by monitoring growth on BSA in the presence of the inhibitors. While pepstatin blocked the activity of all of the Saps tested, the human immunodeficiency virus protease inhibitors ritonavir and saquinavir inhibited growth of the strains expressing Sap1p to Sap3p and Sap1p, respectively, but not that of strains expressing other Saps. Therefore, the strain set can be used to test the activity of new protease inhibitors against individual C. albicans Sap isoenzymes by their ability to block the growth of the pathogen.
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