<i>Candida albicans</i> Hexokinase 2 Challenges the <i>Saccharomyces cerevisiae</i> Moonlight Protein Model
Survival of the pathogenic yeast <i>Candida albicans</i> depends upon assimilation of fermentable and non-fermentable carbon sources detected in host microenvironments. Among the various carbon sources encountered in a human body, glucose is the primary source of energy. Its effective de...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/9/4/848 |
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| author | Romain Laurian Jade Ravent Karine Dementhon Marc Lemaire Alexandre Soulard Pascale Cotton |
| author_facet | Romain Laurian Jade Ravent Karine Dementhon Marc Lemaire Alexandre Soulard Pascale Cotton |
| author_sort | Romain Laurian |
| collection | DOAJ |
| description | Survival of the pathogenic yeast <i>Candida albicans</i> depends upon assimilation of fermentable and non-fermentable carbon sources detected in host microenvironments. Among the various carbon sources encountered in a human body, glucose is the primary source of energy. Its effective detection, metabolism and prioritization via glucose repression are primordial for the metabolic adaptation of the pathogen. In <i>C. albicans,</i> glucose phosphorylation is mainly performed by the hexokinase 2 (<i>Ca</i>Hxk2). In addition, in the presence of glucose, <i>Ca</i>HxK2 migrates in the nucleus and contributes to the glucose repression signaling pathway. Based on the known dual function of the <i>Saccharomyces cerevisiae</i> hexokinase 2 (<i>Sc</i>Hxk2), we intended to explore the impact of both enzymatic and regulatory functions of <i>Ca</i>Hxk2 on virulence, using a site-directed mutagenesis approach. We show that the conserved aspartate residue at position 210, implicated in the interaction with glucose, is essential for enzymatic and glucose repression functions but also for filamentation and virulence in macrophages. Point mutations and deletion into the <i>N</i>-terminal region known to specifically affect glucose repression in <i>Sc</i>Hxk2 proved to be ineffective in <i>Ca</i>Hxk2. These results clearly show that enzymatic and regulatory functions of the hexokinase 2 cannot be unlinked in <i>C. albicans.</i> |
| first_indexed | 2024-03-10T12:18:38Z |
| format | Article |
| id | doaj.art-b16d07ae67cc4b18b6495ae5e6213b76 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T12:18:38Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-b16d07ae67cc4b18b6495ae5e6213b762023-11-21T15:42:20ZengMDPI AGMicroorganisms2076-26072021-04-019484810.3390/microorganisms9040848<i>Candida albicans</i> Hexokinase 2 Challenges the <i>Saccharomyces cerevisiae</i> Moonlight Protein ModelRomain Laurian0Jade Ravent1Karine Dementhon2Marc Lemaire3Alexandre Soulard4Pascale Cotton5INSA Lyon, CNRS, Université de Lyon, Université Claude Bernard Lyon1, UMR5240 MAP, 69622 Villeurbanne, FranceINSA Lyon, CNRS, Université de Lyon, Université Claude Bernard Lyon1, UMR5240 MAP, 69622 Villeurbanne, FranceUMR-CNRS 5234, Laboratoire de Microbiologie Fondamentale et Pathogénicité, Université de Bordeaux, 33076 Bordeaux, FranceINSA Lyon, CNRS, Université de Lyon, Université Claude Bernard Lyon1, UMR5240 MAP, 69622 Villeurbanne, FranceINSA Lyon, CNRS, Université de Lyon, Université Claude Bernard Lyon1, UMR5240 MAP, 69622 Villeurbanne, FranceINSA Lyon, CNRS, Université de Lyon, Université Claude Bernard Lyon1, UMR5240 MAP, 69622 Villeurbanne, FranceSurvival of the pathogenic yeast <i>Candida albicans</i> depends upon assimilation of fermentable and non-fermentable carbon sources detected in host microenvironments. Among the various carbon sources encountered in a human body, glucose is the primary source of energy. Its effective detection, metabolism and prioritization via glucose repression are primordial for the metabolic adaptation of the pathogen. In <i>C. albicans,</i> glucose phosphorylation is mainly performed by the hexokinase 2 (<i>Ca</i>Hxk2). In addition, in the presence of glucose, <i>Ca</i>HxK2 migrates in the nucleus and contributes to the glucose repression signaling pathway. Based on the known dual function of the <i>Saccharomyces cerevisiae</i> hexokinase 2 (<i>Sc</i>Hxk2), we intended to explore the impact of both enzymatic and regulatory functions of <i>Ca</i>Hxk2 on virulence, using a site-directed mutagenesis approach. We show that the conserved aspartate residue at position 210, implicated in the interaction with glucose, is essential for enzymatic and glucose repression functions but also for filamentation and virulence in macrophages. Point mutations and deletion into the <i>N</i>-terminal region known to specifically affect glucose repression in <i>Sc</i>Hxk2 proved to be ineffective in <i>Ca</i>Hxk2. These results clearly show that enzymatic and regulatory functions of the hexokinase 2 cannot be unlinked in <i>C. albicans.</i>https://www.mdpi.com/2076-2607/9/4/848<i>Candida albicans</i><i>Saccharomyces cerevisiae</i>hexokinase 2glucose repressionhexose kinase activityhyphal transition |
| spellingShingle | Romain Laurian Jade Ravent Karine Dementhon Marc Lemaire Alexandre Soulard Pascale Cotton <i>Candida albicans</i> Hexokinase 2 Challenges the <i>Saccharomyces cerevisiae</i> Moonlight Protein Model Microorganisms <i>Candida albicans</i> <i>Saccharomyces cerevisiae</i> hexokinase 2 glucose repression hexose kinase activity hyphal transition |
| title | <i>Candida albicans</i> Hexokinase 2 Challenges the <i>Saccharomyces cerevisiae</i> Moonlight Protein Model |
| title_full | <i>Candida albicans</i> Hexokinase 2 Challenges the <i>Saccharomyces cerevisiae</i> Moonlight Protein Model |
| title_fullStr | <i>Candida albicans</i> Hexokinase 2 Challenges the <i>Saccharomyces cerevisiae</i> Moonlight Protein Model |
| title_full_unstemmed | <i>Candida albicans</i> Hexokinase 2 Challenges the <i>Saccharomyces cerevisiae</i> Moonlight Protein Model |
| title_short | <i>Candida albicans</i> Hexokinase 2 Challenges the <i>Saccharomyces cerevisiae</i> Moonlight Protein Model |
| title_sort | i candida albicans i hexokinase 2 challenges the i saccharomyces cerevisiae i moonlight protein model |
| topic | <i>Candida albicans</i> <i>Saccharomyces cerevisiae</i> hexokinase 2 glucose repression hexose kinase activity hyphal transition |
| url | https://www.mdpi.com/2076-2607/9/4/848 |
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