Bayot Juliette, Martin Caroline, Chevreux Guillaume, Camadro Jean-Michel, Auchère Françoise
Université Paris Cité, CNRS, Institut Jacques Monod, F-75013 Paris, France.
Biochem J. 2023 Feb 14;480(3):197-217. doi: 10.1042/BCJ20220505.
Candida albicans is an opportunist pathogen responsible for a large spectrum of infections, from superficial mycosis to systemic diseases known as candidiasis. During infection in vivo, Candida albicans must adapt to host microenvironments and this adaptive response is crucial for the survival of this organism, as it facilitates the effective assimilation of alternative carbon sources others than glucose. We performed a global proteomic analysis on the global changes in protein abundance in response to changes in micronutrient levels, and, in parallel, explored changes in the intracellular redox and metabolic status of the cells. We show here that each of the carbon sources considered - glucose, acetate and lactate - induces a unique pattern of response in C. albicans cells, and that some conditions trigger an original and specific adaptive response involving the adaptation of metabolic pathways, but also a complete remodeling of thiol-dependent antioxidant defenses. Protein S-thiolation and the overproduction of reduced glutathione are two components of the response to high glucose concentration. In the presence of acetate, glutathione-dependent oxidative stress occurs, reduced thiol groups bind to proteins, and glutathione is exported out of the cells, these changes probably being triggered by an increase in glutathione-S-transferases. Overall, our results suggest that the role of cellular redox status regulation and defenses against oxidative stress, including the thiol- and glutathione-dependent response, in the adaptive response of C. albicans to alternative carbon sources should be reconsidered.
白色念珠菌是一种机会致病菌，可引发从浅表真菌病到称为念珠菌病的全身性疾病等多种感染。在体内感染过程中，白色念珠菌必须适应宿主微环境，这种适应性反应对该生物体的存活至关重要，因为它有助于有效同化除葡萄糖以外的其他碳源。我们针对微量营养素水平变化所引起的蛋白质丰度的整体变化进行了全局蛋白质组学分析，同时还探究了细胞内氧化还原和代谢状态的变化。我们在此表明，所考虑的每种碳源——葡萄糖、乙酸盐和乳酸盐——都会在白色念珠菌细胞中诱导出独特的反应模式，并且某些条件会引发一种原始且特定的适应性反应，这种反应不仅涉及代谢途径的适应，还涉及硫醇依赖性抗氧化防御的完全重塑。蛋白质S-硫醇化和还原型谷胱甘肽的过量产生是对高葡萄糖浓度反应的两个组成部分。在乙酸盐存在的情况下，会发生谷胱甘肽依赖性氧化应激，还原的硫醇基团与蛋白质结合，谷胱甘肽被输出到细胞外，这些变化可能是由谷胱甘肽-S-转移酶的增加引发的。总体而言，我们的结果表明，应重新考虑细胞氧化还原状态调节以及包括硫醇和谷胱甘肽依赖性反应在内的抗氧化应激防御在白色念珠菌对替代碳源的适应性反应中的作用。
