ArticleThe Journal of biological chemistry2013
Deletion of vacuolar proton-translocating ATPase V(o)a isoforms clarifies the role of vacuolar pH as a determinant of virulence-associated traits in Candida albicans.
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 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- The V-ATPase VJournal of oral microbiology · 2026Article
- The Role of Secretory Pathways inJournal of fungi (Basel, Switzerland) · 2020Review
- Article
- ZnT2 is critical for lysosome acidification and biogenesis during mammary gland involution.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Effects of Disruption of PMC1 in the tfp1∆/∆ Mutant on Calcium Homeostasis, Oxidative and Osmotic Stress Resistance in Candida albicans.Mycopathologia · 2018Article
- Promising Antifungal Targets AgainstFrontiers in cellular and infection microbiology · 2018Review
- Endosomal Trafficking Defects Can Induce Calcium-Dependent Azole Tolerance in Candida albicans.Antimicrobial agents and chemotherapy · 2016Article
- Pleiotropic effects of the vacuolar ABC transporter MLT1 of Candida albicans on cell function and virulence.The Biochemical journal · 2016Article
- Proton Transport and pH Control in Fungi.Advances in experimental medicine and biology · 2016Review
- Presenilin 1 Maintains Lysosomal Ca(2+) Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification.Cell reports · 2015Article
- Candida Biofilms: Development, Architecture, and Resistance.Microbiology spectrum · 2015Review
- Quinacrine inhibits Candida albicans growth and filamentation at neutral pH.Antimicrobial agents and chemotherapy · 2014Article
- The contribution of Candida albicans vacuolar ATPase subunit V₁B, encoded by VMA2, to stress response, autophagy, and virulence is independent of environmental pH.Eukaryotic cell · 2014Article
- Saccharomyces cerevisiae vacuolar H+-ATPase regulation by disassembly and reassembly: one structure and multiple signals.Eukaryotic cell · 2014Review
- Advances in targeting the vacuolar proton-translocating ATPase (V-ATPase) for anti-fungal therapy.Frontiers in pharmacology · 2014Review
- Attenuation of Candida albicans virulence with focus on disruption of its vacuole functions.Journal of oral microbiology · 2014Review
- C. albicans growth, transition, biofilm formation, and gene expression modulation by antimicrobial decapeptide KSL-W.BMC microbiology · 2013Article
- Candida albicans VMA3 is necessary for V-ATPase assembly and function and contributes to secretion and filamentation.Eukaryotic cell · 2013Article
- Impact of environmental conditions on the form and function of Candida albicans biofilms.Eukaryotic cell · 2013Article
- Essential role for vacuolar acidification in Candida albicans virulence.The Journal of biological chemistry · 2013Article
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
Vacuolar proton-translocating ATPase (V-ATPase) is a central regulator of cellular pH homeostasis, and inactivation of all V-ATPase function has been shown to prevent infectivity in Candida albicans. V-ATPase subunit a of the Vo domain (Voa) is present as two fungal isoforms: Stv1p (Golgi) and Vph1p (vacuole). To delineate the individual contribution of Stv1p and Vph1p to C. albicans physiology, we created stv1Δ/Δ and vph1Δ/Δ mutants and compared them to the corresponding reintegrant strains (stv1Δ/ΔR and vph1Δ/ΔR). V-ATPase activity, vacuolar physiology, and in vitro virulence-related phenotypes were unaffected in the stv1Δ/Δ mutant. The vph1Δ/Δ mutant exhibited defective V1Vo assembly and a 90% reduction in concanamycin A-sensitive ATPase activity and proton transport in purified vacuolar membranes, suggesting that the Vph1p isoform is essential for vacuolar V-ATPase activity in C. albicans. The vph1Δ/Δ cells also had abnormal endocytosis and vacuolar morphology and an alkalinized vacuolar lumen (pHvph1Δ/Δ = 6.8 versus pHvph1Δ/ΔR = 5.8) in both yeast cells and hyphae. Secreted protease and lipase activities were significantly reduced, and M199-induced filamentation was impaired in the vph1Δ/Δ mutant. However, the vph1Δ/Δ cells remained competent for filamentation induced by Spider media and YPD, 10% FCS, and biofilm formation and macrophage killing were unaffected in vitro. These studies suggest that different virulence mechanisms differentially rely on acidified vacuoles and that the loss of both vacuolar (Vph1p) and non-vacuolar (Stv1p) V-ATPase activity is necessary to affect in vitro virulence-related phenotypes. As a determinant of C. albicans pathogenesis, vacuolar pH alone may prove less critical than originally assumed.
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