Laurian Romain, Dementhon Karine, Doumèche Bastien, Soulard Alexandre, Noel Thierry, Lemaire Marc, Cotton Pascale
Génétique Moléculaire des Levures, UMR-CNRS 5240 Microbiologie Adaptation et Pathogénie, Université de Lyon - Université Lyon 1, Lyon, France.
Laboratoire de Microbiologie Fondamentale et Pathogénicité, UMR-CNRS 5234, Université de Bordeaux, Bordeaux, France.
Front Microbiol. 2019 Feb 25;10:327. doi: 10.3389/fmicb.2019.00327. eCollection 2019.
The pathogenic yeast 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 hexose kinase system composed of one hexokinase (Hxk2) and two glucokinases (Glk1 and Glk4). Using a set of mutant strains, we found that hexose phosphorylation is mostly performed by Hxk2, 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, Hxk2 migrates in the nucleus and contributes to the glucose repression signaling pathway. In addition, Hxk2 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 and macrophage models. Filamentation, glucose phosphorylation and stress response defects of the hexokinase mutant prevent host killing by . By contributing to metabolic flexibility, stress response and morphogenesis, hexose kinase enzymes play an essential role in the virulence of .
致病性酵母既是人类强大的共生菌，也是病原体，可感染多种器官和身体部位。代谢灵活性促进了这种机会性病原体的感染和共生定植。酵母细胞的存活依赖于对可发酵和不可发酵的局部可用碳源的同化。宿主生态位中葡萄糖和果糖等生理相关糖的含量较低。然而，由于葡萄糖是能量和结构成分生物合成的首选底物，其有效检测和代谢对于病原体的代谢适应至关重要。我们探索并表征了由一种己糖激酶（Hxk2）和两种葡萄糖激酶（Glk1和Glk4）组成的己糖激酶系统。使用一组突变菌株，我们发现己糖磷酸化主要由Hxk2进行，它维持己糖上的生长。我们关于己糖激酶和葡萄糖激酶表达的数据指出在转录水平不存在交叉调节机制以及不同的调节途径。在葡萄糖存在的情况下，Hxk2迁移到细胞核并参与葡萄糖阻遏信号通路。此外，Hxk2参与氧化、渗透和细胞壁应激反应，而葡萄糖激酶在缺氧条件下过表达。己糖磷酸化是丝状化所必需的关键步骤，在己糖激酶突变体中受到影响。该突变体的毒力在小鼠和巨噬细胞模型中明显受到影响。己糖激酶突变体的丝状化、葡萄糖磷酸化和应激反应缺陷阻止了宿主被病原体杀死。通过促进代谢灵活性、应激反应和形态发生，己糖激酶酶在病原体的毒力中起重要作用。
