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1دورية أكاديمية
المؤلفون: Hallie S. Rane, Summer R. Hayek, Jillian E. Frye, Esteban L. Abeyta, Stella M. Bernardo, Karlett J. Parra, Samuel A. Lee
المصدر: Frontiers in Microbiology, Vol 10 (2019)
مصطلحات موضوعية: Candida albicans, cytosolic pH, filamentation, glucose metabolism, pH homeostasis, plasma membrane H+ ATPase, Microbiology, QR1-502
الوصف: Candida albicans occupies diverse ecological niches within the host and must tolerate a wide range of environmental pH. The plasma membrane H+-ATPase Pma1p is the major regulator of cytosolic pH in fungi. Pma1p extrudes protons from the cytosol to maintain neutral-to-alkaline pH and is a potential drug target due to its essentiality and fungal specificity. We characterized mutants in which one allele of PMA1 has been deleted and the other truncated by 18–38 amino acids. Increasing C-terminal truncation caused corresponding decreases in plasma membrane ATPase-specific activity and cytosolic pH. Pma1p is regulated by glucose: glucose rapidly activates the ATPase, causing a sharp increase in cytosolic pH. Increasing Pma1p truncation severely impaired this glucose response. Pma1p truncation also altered cation responses, disrupted vacuolar morphology and pH, and reduced filamentation competence. Early studies of cytosolic pH and filamentation have described a rapid, transient alkalinization of the cytosol preceding germ tube formation; Pma1p has been proposed as a regulator of this process. We find Pma1p plays a role in the establishment of cell polarity, and distribution of Pma1p is non-homogenous in emerging hyphae. These findings suggest a role of PMA1 in cytosolic alkalinization and in the specialized form of polarized growth that is filamentation.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/article/10.3389/fmicb.2019.01012/fullTest; https://doaj.org/toc/1664-302XTest
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2دورية أكاديمية
المؤلفون: Summer R. Hayek, Hallie S. Rane, Karlett J. Parra
المصدر: Frontiers in Physiology, Vol 10 (2019)
مصطلحات موضوعية: V-ATPase, glycolysis, glucose, metabolism, TORC1, yeast, Physiology, QP1-981
الوصف: The ability of cells to adapt to fluctuations in glucose availability is crucial for their survival and involves the vacuolar proton-translocating ATPase (V-ATPase), a proton pump found in all eukaryotes. V-ATPase hydrolyzes ATP via its V1 domain and uses the energy released to transport protons across membranes via its Vo domain. This activity is critical for pH homeostasis and generation of a membrane potential that drives cellular metabolism. A number of stimuli have been reported to alter V-ATPase assembly in yeast and higher eukaryotes. Glucose flux is one of the strongest and best-characterized regulators of V-ATPase; this review highlights current models explaining how glycolysis and V-ATPase are coordinated in both the Saccharomyces cerevisiae model fungus and in mammalian systems. Glucose-dependent assembly and trafficking of V-ATPase, V-ATPase-dependent modulations in glycolysis, and the recent discovery that glucose signaling through V-ATPase acts as a molecular switch to dictate anabolic versus catabolic metabolism are discussed. Notably, metabolic plasticity and altered glycolytic flux are critical drivers of numerous human pathologies, and the expression and activity of V-ATPase is often altered in disease states or can be pharmacologically manipulated as treatment. This overview will specifically discuss connections between V-ATPase and glycolysis in cancer.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/article/10.3389/fphys.2019.00127/fullTest; https://doaj.org/toc/1664-042XTest
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3دورية أكاديمية
المؤلفون: Anitha Sundararajan, Hallie S Rane, Thiruvarangan Ramaraj, Johnny Sena, Amy B Howell, Stella M Bernardo, Faye D Schilkey, Samuel A Lee
المصدر: PLoS ONE, Vol 13, Iss 8, p e0201969 (2018)
الوصف: Candida albicans is one of the most common causes of hospital-acquired urinary tract infections (UTIs). However, azoles are poorly active against biofilms, echinocandins do not achieve clinically useful urinary concentrations, and amphotericin B exhibits severe toxicities. Thus, novel strategies are needed to prevent Candida UTIs, which are often associated with urinary catheter biofilms. We previously demonstrated that cranberry-derived proanthocyanidins (PACs) prevent C. albicans biofilm formation in an in vitro urinary model. To elucidate functional pathways unique to urinary biofilm development and PAC inhibition, we investigated the transcriptome of C. albicans in artificial urine (AU), with and without PACs. C. albicans biofilm and planktonic cells were cultivated with or without PACs. Genome-wide expression analysis was performed by RNA sequencing. Differentially expressed genes were determined using DESeq2 software; pathway analysis was performed using Cytoscape. Approximately 2,341 of 6,444 total genes were significantly expressed in biofilm relative to planktonic cells. Functional pathway analysis revealed that genes involved in filamentation, adhesion, drug response and transport were up-regulated in urinary biofilms. Genes involved in carbon and nitrogen metabolism and nutrient response were down-regulated. In PAC-treated urinary biofilms compared to untreated control biofilms, 557 of 6,444 genes had significant changes in gene expression. Genes downregulated in PAC-treated biofilms were implicated in iron starvation and adhesion pathways. Although urinary biofilms share key features with biofilms formed in other environments, many genes are uniquely expressed in urinary biofilms. Cranberry-derived PACs interfere with the expression of iron acquisition and adhesion genes within urinary biofilms.
العلاقة: http://europepmc.org/articles/PMC6082538?pdf=renderTest; https://doaj.org/toc/1932-6203Test; https://doaj.org/article/30005a9217cd4e88bc5875d58219da38Test
الإتاحة: https://doi.org/10.1371/journal.pone.0201969Test
https://doaj.org/article/30005a9217cd4e88bc5875d58219da38Test -
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المؤلفون: Karlett J. Parra, Sarah Fogarty, Jared Rutter, Hallie S. Rane, Liubo Li, Patrick G. Harran, Yeyun Ouyang, Francesco Manoni, Yu-Chan Chen
المصدر: Journal of Natural Products. 83:3381-3386
مصطلحات موضوعية: Vacuolar Proton-Translocating ATPases, Pharmaceutical Science, Saccharomyces cerevisiae, 01 natural sciences, Analytical Chemistry, Drug Discovery, Humans, Enzyme Inhibitors, Cytotoxicity, IC50, Fluorescent Dyes, Pharmacology, Molecular Structure, 010405 organic chemistry, Cell growth, Chemistry, Organic Chemistry, Hydrogen-Ion Concentration, Fluorescence, Molecular biology, Yeast, In vitro, 0104 chemical sciences, 010404 medicinal & biomolecular chemistry, Vacuolar acidification, Complementary and alternative medicine, Cell culture, Molecular Medicine, Macrolides
الوصف: Callyspongiolide is a marine-derived macrolide that kills cells in a caspase-independent manner. NCI COMPARE analysis of human tumor cell line toxicity data for synthetic callyspongiolide indicated that its pattern of cytotoxicity correlated with that seen for concanamycin A, an inhibitor of the vacuolar-type H+-ATPase (V-ATPase). Using yeast as a model system, we report that treatment with synthetic callyspongiolide phenocopied a loss of V-ATPase activity including (1) inability to grow on a nonfermentable carbon source, (2) rescue of cell growth via supplementation with Fe2+, (3) pH-sensitive growth, and (4) a vacuolar acidification defect visualized using the fluorescent dye quinacrine. Crucially, in an in vitro assay, callyspongiolide was found to dose-dependently inhibit yeast V-ATPase (IC50 = 10 nM). Together, these data identify callyspongiolide as a new and highly potent V-ATPase inhibitor. Notably, callyspongiolide is the first V-ATPase inhibitor known to be expelled by Pdr5p.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::48aa26afb38183eb93e77fa28481ded0Test
https://doi.org/10.1021/acs.jnatprod.0c00813Test -
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المؤلفون: Jillian E. Frye, Karlett J. Parra, Samuel A. Lee, Summer R. Hayek, Esteban Abeyta, Hallie S. Rane, Stella M. Bernardo
المصدر: Frontiers in Microbiology
Frontiers in Microbiology, Vol 10 (2019)مصطلحات موضوعية: Microbiology (medical), cytosolic pH, glucose metabolism, ATPase, lcsh:QR1-502, Germ tube, Microbiology, lcsh:Microbiology, plasma membrane H+ ATPase, 03 medical and health sciences, Filamentation, Candida albicans, Cell polarity, Original Research, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, Chemistry, pH homeostasis, Metabolism, biology.organism_classification, Cell biology, filamentation, Cytosol, biology.protein, Homeostasis
الوصف: Candida albicans occupies diverse ecological niches within the host and must tolerate a wide range of environmental pH. The plasma membrane H+-ATPase Pma1p is the major regulator of cytosolic pH in fungi. Pma1p extrudes protons from the cytosol to maintain neutral-to-alkaline pH and is a potential drug target due to its essentiality and fungal specificity. We characterized mutants in which one allele of PMA1 has been deleted and the other truncated by 18–38 amino acids. Increasing C-terminal truncation caused corresponding decreases in plasma membrane ATPase-specific activity and cytosolic pH. Pma1p is regulated by glucose: glucose rapidly activates the ATPase, causing a sharp increase in cytosolic pH. Increasing Pma1p truncation severely impaired this glucose response. Pma1p truncation also altered cation responses, disrupted vacuolar morphology and pH, and reduced filamentation competence. Early studies of cytosolic pH and filamentation have described a rapid, transient alkalinization of the cytosol preceding germ tube formation; Pma1p has been proposed as a regulator of this process. We find Pma1p plays a role in the establishment of cell polarity, and distribution of Pma1p is non-homogenous in emerging hyphae. These findings suggest a role of PMA1 in cytosolic alkalinization and in the specialized form of polarized growth that is filamentation.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3a155460bb828141f4574f6ea7a5f761Test
https://doi.org/10.3389/fmicb.2019.01012Test -
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المؤلفون: Karlett J. Parra, Summer R. Hayek, Hallie S. Rane
المصدر: Frontiers in Physiology
Frontiers in Physiology, Vol 10 (2019)مصطلحات موضوعية: 0301 basic medicine, Physiology, ATPase, Saccharomyces cerevisiae, V-ATPase, Review, yeast, lcsh:Physiology, 03 medical and health sciences, Physiology (medical), cancer, Glycolysis, human, glucose, lcsh:QP1-981, 030102 biochemistry & molecular biology, biology, Chemistry, Catabolism, Metabolism, glycolysis, biology.organism_classification, TORC1, Cell biology, 030104 developmental biology, biology.protein, metabolism, Flux (metabolism), Homeostasis
الوصف: The ability of cells to adapt to fluctuations in glucose availability is crucial for their survival and involves the vacuolar proton-translocating ATPase (V-ATPase), a proton pump found in all eukaryotes. V-ATPase hydrolyzes ATP via its V1 domain and uses the energy released to transport protons across membranes via its Vo domain. This activity is critical for pH homeostasis and generation of a membrane potential that drives cellular metabolism. A number of stimuli have been reported to alter V-ATPase assembly in yeast and higher eukaryotes. Glucose flux is one of the strongest and best-characterized regulators of V-ATPase; this review highlights current models explaining how glycolysis and V-ATPase are coordinated in both the Saccharomyces cerevisiae model fungus and in mammalian systems. Glucose-dependent assembly and trafficking of V-ATPase, V-ATPase-dependent modulations in glycolysis, and the recent discovery that glucose signaling through V-ATPase acts as a molecular switch to dictate anabolic versus catabolic metabolism are discussed. Notably, metabolic plasticity and altered glycolytic flux are critical drivers of numerous human pathologies, and the expression and activity of V-ATPase is often altered in disease states or can be pharmacologically manipulated as treatment. This overview will specifically discuss connections between V-ATPase and glycolysis in cancer.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53b310d1692954c9c96b7741f8930440Test
https://doi.org/10.3389/fphys.2019.00127Test -
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المؤلفون: Hallie S. Rane, Summer R. Hayek, Jillian E. Frye, Esteban L. Abeyta, Stella M. Bernardo, Karlett J. Parra, Samuel A. Lee
مصطلحات موضوعية: Microbiology, Microbial Genetics, Microbial Ecology, Mycology, Candida albicans, cytosolic pH, filamentation, glucose metabolism, pH homeostasis, plasma membrane H+ ATPase
الوصف: Candida albicans occupies diverse ecological niches within the host and must tolerate a wide range of environmental pH. The plasma membrane H + -ATPase Pma1p is the major regulator of cytosolic pH in fungi. Pma1p extrudes protons from the cytosol to maintain neutral-to-alkaline pH and is a potential drug target due to its essentiality and fungal specificity. We characterized mutants in which one allele of PMA1 has been deleted and the other truncated by 18–38 amino acids. Increasing C-terminal truncation caused corresponding decreases in plasma membrane ATPase-specific activity and cytosolic pH. Pma1p is regulated by glucose: glucose rapidly activates the ATPase, causing a sharp increase in cytosolic pH. Increasing Pma1p truncation severely impaired this glucose response. Pma1p truncation also altered cation responses, disrupted vacuolar morphology and pH, and reduced filamentation competence. Early studies of cytosolic pH and filamentation have described a rapid, transient alkalinization of the cytosol preceding germ tube formation; Pma1p has been proposed as a regulator of this process. We find Pma1p plays a role in the establishment of cell polarity, and distribution of Pma1p is non-homogenous in emerging hyphae. These findings suggest a role of PMA1 in cytosolic alkalinization and in the specialized form of polarized growth that is filamentation.
الإتاحة: https://doi.org/10.3389/fmicb.2019.01012.s004Test
https://figshare.com/articles/dataset/Table_3_Candida_albicans_Pma1p_Contributes_to_Growth_pH_Homeostasis_and_Hyphal_Formation_xlsx/8100245Test -
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المؤلفون: Hallie S. Rane, Summer R. Hayek, Jillian E. Frye, Esteban L. Abeyta, Stella M. Bernardo, Karlett J. Parra, Samuel A. Lee
مصطلحات موضوعية: Microbiology, Microbial Genetics, Microbial Ecology, Mycology, Candida albicans, cytosolic pH, filamentation, glucose metabolism, pH homeostasis, plasma membrane H+ ATPase
الوصف: Candida albicans occupies diverse ecological niches within the host and must tolerate a wide range of environmental pH. The plasma membrane H + -ATPase Pma1p is the major regulator of cytosolic pH in fungi. Pma1p extrudes protons from the cytosol to maintain neutral-to-alkaline pH and is a potential drug target due to its essentiality and fungal specificity. We characterized mutants in which one allele of PMA1 has been deleted and the other truncated by 18–38 amino acids. Increasing C-terminal truncation caused corresponding decreases in plasma membrane ATPase-specific activity and cytosolic pH. Pma1p is regulated by glucose: glucose rapidly activates the ATPase, causing a sharp increase in cytosolic pH. Increasing Pma1p truncation severely impaired this glucose response. Pma1p truncation also altered cation responses, disrupted vacuolar morphology and pH, and reduced filamentation competence. Early studies of cytosolic pH and filamentation have described a rapid, transient alkalinization of the cytosol preceding germ tube formation; Pma1p has been proposed as a regulator of this process. We find Pma1p plays a role in the establishment of cell polarity, and distribution of Pma1p is non-homogenous in emerging hyphae. These findings suggest a role of PMA1 in cytosolic alkalinization and in the specialized form of polarized growth that is filamentation.
الإتاحة: https://doi.org/10.3389/fmicb.2019.01012.s001Test
https://figshare.com/articles/dataset/Data_Sheet_1_Candida_albicans_Pma1p_Contributes_to_Growth_pH_Homeostasis_and_Hyphal_Formation_PDF/8100236Test -
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المؤلفون: Stella M. Bernardo, Samuel A. Lee, Hallie S. Rane, Alba Chavez-Dozal
المصدر: Eukaryotic Cell. 14:1228-1239
مصطلحات موضوعية: Aspartic Acid Proteases, Hydrolases, Green Fluorescent Proteins, Mutant, Hyphae, Exocyst, Microbiology, Fungal Proteins, Filamentation, Cell Wall, Candida albicans, Secretion, Retractions, Molecular Biology, Polarisome, Fungal protein, Microbial Viability, biology, Chitinases, Spitzenkörper, Adhesiveness, Lipase, General Medicine, Tetracycline, biology.organism_classification, Cell biology, Protein Subunits, Phenotype, Doxycycline, Mutation
الوصف: In prior studies of exocyst-mediated late secretion in Candida albicans , we have determined that Sec6 contributes to cell wall integrity, secretion, and filamentation. A conditional mutant lacking SEC6 expression exhibits markedly reduced lateral hyphal branching. In addition, lack of the related t-SNAREs Sso2 and Sec9 also leads to defects in secretion and filamentation. To further understand the role of the exocyst in the fundamental processes of polarized secretion and filamentation in C. albicans , we studied the exocyst subunit Sec15. Since Saccharomyces cerevisiae SEC15 is essential for viability, we generated a C. albicans conditional mutant strain in which SEC15 was placed under the control of a tetracycline-regulated promoter. In the repressed state, cell death occurred after 5 h in the tetR-SEC15 strain. Prior to this time point, the tetR-SEC15 mutant was markedly defective in Sap and lipase secretion and demonstrated increased sensitivity to Zymolyase and chitinase. Notably, tetR-SEC15 mutant hyphae were characterized by a hyperbranching phenotype, in direct contrast to strain tetR-SEC6, which had minimal lateral branching. We further studied the localization of the Spitzenkörper, polarisomes, and exocysts in the tetR-SEC15 and tetR-SEC6 mutants during filamentation. Mlc1-GFP (marking the Spitzenkörper), Spa2-GFP (the polarisome), and Exo70-GFP (exocyst) localizations were normal in the tetR-SEC6 mutant, whereas these structures were mislocalized in the tetR-SEC15 mutant. Following alleviation of gene repression by removing doxycycline, first Spitzenkörper, then polarisome, and finally exocyst localizations were recovered sequentially. These results indicate that the exocyst subunits Sec15 and Sec6 have distinct roles in mediating polarized secretion and filamentation in C. albicans .
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5d0828141c086875f802b294853aed73Test
https://doi.org/10.1128/ec.00147-15Test -
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المؤلفون: Faye D. Schilkey, Hallie S. Rane, Stella M. Bernardo, Thiruvarangan Ramaraj, Johnny Sena, Anitha Sundararajan, Samuel A. Lee, Amy B. Howell
المصدر: PLoS ONE, Vol 13, Iss 8, p e0201969 (2018)
PLoS ONEمصطلحات موضوعية: 0301 basic medicine, Gene Expression, lcsh:Medicine, Yeast and Fungal Models, Pathogenesis, Pathology and Laboratory Medicine, Biochemistry, Transcriptome, Gene Expression Regulation, Fungal, Gene expression, Candida albicans, Medicine and Health Sciences, Gene Regulatory Networks, lcsh:Science, Candida, 2. Zero hunger, Regulation of gene expression, Fungal Pathogens, Multidisciplinary, biology, Chemistry, Candidiasis, High-Throughput Nucleotide Sequencing, Eukaryota, Genomics, Corpus albicans, Vaccinium macrocarpon, Experimental Organism Systems, Medical Microbiology, Urinary Tract Infections, Pathogens, Transcriptome Analysis, Research Article, Biotechnology, Catheters, 030106 microbiology, Mycology, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Genetics, Proanthocyanidins, Gene, Microbial Pathogens, Plant Extracts, Gene Expression Profiling, lcsh:R, Biofilm, Organisms, Fungi, Biology and Life Sciences, Computational Biology, Biological Transport, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Genome Analysis, Yeast, Gene expression profiling, Metabolism, Biofilms, Medical Devices and Equipment, lcsh:Q
الوصف: Candida albicans is one of the most common causes of hospital-acquired urinary tract infections (UTIs). However, azoles are poorly active against biofilms, echinocandins do not achieve clinically useful urinary concentrations, and amphotericin B exhibits severe toxicities. Thus, novel strategies are needed to prevent Candida UTIs, which are often associated with urinary catheter biofilms. We previously demonstrated that cranberry-derived proanthocyanidins (PACs) prevent C. albicans biofilm formation in an in vitro urinary model. To elucidate functional pathways unique to urinary biofilm development and PAC inhibition, we investigated the transcriptome of C. albicans in artificial urine (AU), with and without PACs. C. albicans biofilm and planktonic cells were cultivated with or without PACs. Genome-wide expression analysis was performed by RNA sequencing. Differentially expressed genes were determined using DESeq2 software; pathway analysis was performed using Cytoscape. Approximately 2,341 of 6,444 total genes were significantly expressed in biofilm relative to planktonic cells. Functional pathway analysis revealed that genes involved in filamentation, adhesion, drug response and transport were up-regulated in urinary biofilms. Genes involved in carbon and nitrogen metabolism and nutrient response were down-regulated. In PAC-treated urinary biofilms compared to untreated control biofilms, 557 of 6,444 genes had significant changes in gene expression. Genes downregulated in PAC-treated biofilms were implicated in iron starvation and adhesion pathways. Although urinary biofilms share key features with biofilms formed in other environments, many genes are uniquely expressed in urinary biofilms. Cranberry-derived PACs interfere with the expression of iron acquisition and adhesion genes within urinary biofilms.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7bccf995f27032eccc8c4e28e0c3835cTest
http://europepmc.org/articles/PMC6082538?pdf=renderTest
النص الكامل