Hexokinase and Glucokinases Are Essential for Fitness and Virulence in the Pathogenic Yeast Candida albicans
The pathogenic yeast Candida albicans is both a powerful commensal and a pathogen of humans that can infect wide range of organs and body sites. Metabolic flexibility promotes infection and commensal colonization by this opportunistic pathogen. Yeast cell survival depends upon assimilation of fermen...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.00327/full |
| _version_ | 1828939423786467328 |
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| author | Romain Laurian Karine Dementhon Bastien Doumèche Alexandre Soulard Thierry Noel Marc Lemaire Pascale Cotton |
| author_facet | Romain Laurian Karine Dementhon Bastien Doumèche Alexandre Soulard Thierry Noel Marc Lemaire Pascale Cotton |
| author_sort | Romain Laurian |
| collection | DOAJ |
| description | The pathogenic yeast Candida albicans is both a powerful commensal and a pathogen of humans that can infect wide range of organs and body sites. Metabolic flexibility promotes infection and commensal colonization by this opportunistic pathogen. Yeast cell survival depends upon assimilation of fermentable and non-fermentable locally available carbon sources. Physiologically relevant sugars like glucose and fructose are present at low levels in host niches. However, because glucose is the preferred substrate for energy and biosynthesis of structural components, its efficient detection and metabolism are fundamental for the metabolic adaptation of the pathogen. We explored and characterized the C. albicans hexose kinase system composed of one hexokinase (CaHxk2) and two glucokinases (CaGlk1 and CaGlk4). Using a set of mutant strains, we found that hexose phosphorylation is mostly performed by CaHxk2, which sustains growth on hexoses. Our data on hexokinase and glucokinase expression point out an absence of cross regulation mechanisms at the transcription level and different regulatory pathways. In the presence of glucose, CaHxk2 migrates in the nucleus and contributes to the glucose repression signaling pathway. In addition, CaHxk2 participates in oxidative, osmotic and cell wall stress responses, while glucokinases are overexpressed under hypoxia. Hexose phosphorylation is a key step necessary for filamentation that is affected in the hexokinase mutant. Virulence of this mutant is clearly impacted in the Galleria mellonella and macrophage models. Filamentation, glucose phosphorylation and stress response defects of the hexokinase mutant prevent host killing by C. albicans. By contributing to metabolic flexibility, stress response and morphogenesis, hexose kinase enzymes play an essential role in the virulence of C. albicans. |
| first_indexed | 2024-12-14T03:01:05Z |
| format | Article |
| id | doaj.art-207b663ed0bd4425acf005d6f1d8c2bd |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-14T03:01:05Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-207b663ed0bd4425acf005d6f1d8c2bd2022-12-21T23:19:30ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-02-011010.3389/fmicb.2019.00327433316Hexokinase and Glucokinases Are Essential for Fitness and Virulence in the Pathogenic Yeast Candida albicansRomain Laurian0Karine Dementhon1Bastien Doumèche2Alexandre Soulard3Thierry Noel4Marc Lemaire5Pascale Cotton6Génétique Moléculaire des Levures, UMR-CNRS 5240 Microbiologie Adaptation et Pathogénie, Université de Lyon – Université Lyon 1, Lyon, FranceLaboratoire de Microbiologie Fondamentale et Pathogénicité, UMR-CNRS 5234, Université de Bordeaux, Bordeaux, FranceInstitut de Chimie et Biochimie Moléculaires et Supramoléculaires, Université de Lyon – Université Lyon 1, Lyon, FranceGénétique Moléculaire des Levures, UMR-CNRS 5240 Microbiologie Adaptation et Pathogénie, Université de Lyon – Université Lyon 1, Lyon, FranceLaboratoire de Microbiologie Fondamentale et Pathogénicité, UMR-CNRS 5234, Université de Bordeaux, Bordeaux, FranceGénétique Moléculaire des Levures, UMR-CNRS 5240 Microbiologie Adaptation et Pathogénie, Université de Lyon – Université Lyon 1, Lyon, FranceGénétique Moléculaire des Levures, UMR-CNRS 5240 Microbiologie Adaptation et Pathogénie, Université de Lyon – Université Lyon 1, Lyon, FranceThe pathogenic yeast Candida albicans is both a powerful commensal and a pathogen of humans that can infect wide range of organs and body sites. Metabolic flexibility promotes infection and commensal colonization by this opportunistic pathogen. Yeast cell survival depends upon assimilation of fermentable and non-fermentable locally available carbon sources. Physiologically relevant sugars like glucose and fructose are present at low levels in host niches. However, because glucose is the preferred substrate for energy and biosynthesis of structural components, its efficient detection and metabolism are fundamental for the metabolic adaptation of the pathogen. We explored and characterized the C. albicans hexose kinase system composed of one hexokinase (CaHxk2) and two glucokinases (CaGlk1 and CaGlk4). Using a set of mutant strains, we found that hexose phosphorylation is mostly performed by CaHxk2, which sustains growth on hexoses. Our data on hexokinase and glucokinase expression point out an absence of cross regulation mechanisms at the transcription level and different regulatory pathways. In the presence of glucose, CaHxk2 migrates in the nucleus and contributes to the glucose repression signaling pathway. In addition, CaHxk2 participates in oxidative, osmotic and cell wall stress responses, while glucokinases are overexpressed under hypoxia. Hexose phosphorylation is a key step necessary for filamentation that is affected in the hexokinase mutant. Virulence of this mutant is clearly impacted in the Galleria mellonella and macrophage models. Filamentation, glucose phosphorylation and stress response defects of the hexokinase mutant prevent host killing by C. albicans. By contributing to metabolic flexibility, stress response and morphogenesis, hexose kinase enzymes play an essential role in the virulence of C. albicans.https://www.frontiersin.org/article/10.3389/fmicb.2019.00327/fullCandida albicanshexokinaseglucokinaseglycolysisglucose repressionhyphal transition |
| spellingShingle | Romain Laurian Karine Dementhon Bastien Doumèche Alexandre Soulard Thierry Noel Marc Lemaire Pascale Cotton Hexokinase and Glucokinases Are Essential for Fitness and Virulence in the Pathogenic Yeast Candida albicans Frontiers in Microbiology Candida albicans hexokinase glucokinase glycolysis glucose repression hyphal transition |
| title | Hexokinase and Glucokinases Are Essential for Fitness and Virulence in the Pathogenic Yeast Candida albicans |
| title_full | Hexokinase and Glucokinases Are Essential for Fitness and Virulence in the Pathogenic Yeast Candida albicans |
| title_fullStr | Hexokinase and Glucokinases Are Essential for Fitness and Virulence in the Pathogenic Yeast Candida albicans |
| title_full_unstemmed | Hexokinase and Glucokinases Are Essential for Fitness and Virulence in the Pathogenic Yeast Candida albicans |
| title_short | Hexokinase and Glucokinases Are Essential for Fitness and Virulence in the Pathogenic Yeast Candida albicans |
| title_sort | hexokinase and glucokinases are essential for fitness and virulence in the pathogenic yeast candida albicans |
| topic | Candida albicans hexokinase glucokinase glycolysis glucose repression hyphal transition |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.00327/full |
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