ArticleThe Journal of biological chemistry2013
Essential role for vacuolar acidification in Candida albicans virulence.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Histone deacetylase-mediated regulation of endolysosomal pH.The Journal of biological chemistry · 2018Pooled it
- Linking endo-lysosomal pH, sterol, and trafficking to neurodegenerative disease.FEMS yeast research · 2025Review
- Aloin remodels the cell wall of Candida albicans to reduce its hyphal virulence against oral candidiasis.Applied microbiology and biotechnology · 2025Article
- Carvacrol-Induced Vacuole Dysfunction and Morphological Consequences inMicroorganisms · 2023Article
- The hybrid RAVE complex plays V-ATPase-dependent and -independent pathobiological roles in Cryptococcus neoformans.PLoS pathogens · 2023Article
- Article
- The Investigation of Thymol Formulations Containing Poloxamer 407 and Hydroxypropyl Methylcellulose to InhibitPharmaceuticals (Basel, Switzerland) · 2022Article
- Magnesium impairs Candida albicans immune evasion by reduced hyphal damage, enhanced β-glucan exposure and altered vacuole homeostasis.PloS one · 2022Article
- Investigating the Antifungal Mechanism of Action of Polygodial by Phenotypic Screening inInternational journal of molecular sciences · 2021Article
- The Importance of Vacuolar Ion Homeostasis and Trafficking in Hyphal Development and Virulence inFrontiers in microbiology · 2021Review
- Novel Antifungal Agents and Their Activity againstJournal of fungi (Basel, Switzerland) · 2020Review
- The Role of Secretory Pathways inJournal of fungi (Basel, Switzerland) · 2020Review
- Essential Role for the Phosphatidylinositol 3,5-Bisphosphate Synthesis Complex in Caspofungin Tolerance and Virulence inAntimicrobial agents and chemotherapy · 2019Article
- Vacuolar proton-translocating ATPase is required for antifungal resistance and virulence of Candida glabrata.PloS one · 2019Article
- FcRav2, a gene with a ROGDI domain involved in Fusarium head blight and crown rot on durum wheat caused by Fusarium culmorum.Molecular plant pathology · 2018Article
- Promising Antifungal Targets AgainstFrontiers in cellular and infection microbiology · 2018Review
- How alkalinization drives fungal pathogenicity.PLoS pathogens · 2017Review
- pH-Dependant Antifungal Activity of Valproic Acid against the Human Fungal PathogenFrontiers in microbiology · 2017Article
- Antagonism of Fluconazole and a Proton Pump Inhibitor against Candida albicans.Antimicrobial agents and chemotherapy · 2016Article
- Proton Transport and pH Control in Fungi.Advances in experimental medicine and biology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Fungal infections are on the rise, with mortality above 30% in patients with septic Candida infections. Mutants lacking V-ATPase activity are avirulent and fail to acidify endomembrane compartments, exhibiting pleiotropic defects in secretory, endosomal, and vacuolar pathways. However, the individual contribution of organellar acidification to virulence and its associated traits is not known. To dissect their separate roles in Candida albicans pathogenicity we generated knock-out strains for the V0 subunit a genes VPH1 and STV1, which target the vacuole and secretory pathway, respectively. While the two subunits were redundant in many vma phenotypes, such as alkaline pH sensitivity, calcium homeostasis, respiratory defects, and cell wall integrity, we observed a unique contribution of VPH1. Specifically, vph1Δ was defective in acidification of the vacuole and its dependent functions, such as metal ion sequestration as evidenced by hypersensitivity to Zn(2+) toxicity, whereas stv1Δ resembled wild type. In growth conditions that elicit morphogenic switching, vph1Δ was defective in forming hyphae whereas stv1Δ was normal or only modestly impaired. Host cell interactions were evaluated in vitro using the Caco-2 model of intestinal epithelial cells, and murine macrophages. Like wild type, stv1Δ was able to inflict cellular damage in Caco-2 and macrophage cells, as assayed by LDH release, and escape by filamentation. In contrast, vph1Δ resembled a vma7Δ mutant, with significant attenuation in host cell damage. Finally, we show that VPH1 is required for fungal virulence in a murine model of systemic infection. Our results suggest that vacuolar acidification has an essential function in the ability of C. albicans to form hyphae and establish infection.
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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.