ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Candida albicans secreted aspartic proteases 4-6 induce apoptosis of epithelial cells by a novel Trojan horse mechanism.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 66 citations in OpenAlex.
- Paralogs of thebioRxiv : the preprint server for biology · 2026Article
- Candida albicans aspartyl protease (Sap6) inhibits neutrophil function via a "Trojan horse" mechanism.Scientific reports · 2025Article
- Fungal Als proteins hijack host death effector domains to promote inflammasome signaling.Nature communications · 2025Article
- Darunavir: A Versatile Protease Inhibitor against Microbial Infections.Current drug discovery technologies · 2025Review
- Secreted Aspartic Proteinases: Key Factors inInternational journal of molecular sciences · 2024Review
- Computational modelling of the antimicrobial peptides Cruzioseptin-4 extracted from the frog Cruziohyla calcarifer and Pictuseptin-1 extracted from the frog Boana picturata.Scientific reports · 2024Article
- Exploring the effects of culture conditions on Yapsin (Open life sciences · 2024Article
- Promising immunotherapeutic targets for treating candidiasis.Frontiers in cellular and infection microbiology · 2024Review
- The Yeast and Hypha Phases ofAnimals : an open access journal from MDPI · 2023Article
- The Changes in Mitochondrial Morphology and Physiology Accompanying Apoptosis inInternational journal of molecular sciences · 2023Article
- Characterization of Aspartic Proteases fromJournal of fungi (Basel, Switzerland) · 2023Article
- More than Just Protein Degradation: The Regulatory Roles and Moonlighting Functions of Extracellular Proteases Produced by Fungi Pathogenic for Humans.Journal of fungi (Basel, Switzerland) · 2023Review
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- Reactive Oxygen Species Mediate 6c-Induced Mitochondrial and Lysosomal Dysfunction, Autophagic Cell Death, and DNA Damage in Hepatocellular Carcinoma.International journal of molecular sciences · 2021Article
- Candidalysin triggers epithelial cellular stresses that induce necrotic death.Cellular microbiology · 2021Article
- Mass Spectrometry-Based Proteomic and Immunoproteomic Analyses of theJournal of fungi (Basel, Switzerland) · 2021Article
- Programmed Cell Death: Central Player in Fungal Infections.Trends in cell biology · 2021Review
- Partridge and embryonated partridge egg as new preclinical models for candidiasis.Scientific reports · 2021Article
- A unique aspartyl protease gene expansion in Talaromyces marneffei plays a role in growth inside host phagocytes.Virulence · 2019Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.