Emergence of Candida glabrata, which causes potential life-threatening invasive candidiasis, has been widely associated with high morbidity and mortality. In order to cause disease in vivo, a robust and highly efficient metabolic adaptation is crucial for the survival of this fungal pathogen in human host. In fact, reprogramming of the carbon metabolism is believed to be indispensable for phagocytosed C. glabrata within glucose deprivation condition during infection. In this study, the metabolic responses of C. glabrata under acetate growth condition was explored using high-throughput transcriptomic and proteomic approaches. Collectively, a total of 1482 transcripts (26.96%) and 242 proteins (24.69%) were significantly up- or down-regulated. Both transcriptome and proteome data revealed that the regulation of alternative carbon metabolism in C. glabrata resembled other fungal pathogens such as Candida albicans and Cryptococcus neoformans, with up-regulation of many proteins and transcripts from the glyoxylate cycle and gluconeogenesis, namely isocitrate lyase (ICL1), malate synthase (MLS1), phosphoenolpyruvate carboxykinase (PCK1) and fructose 1,6-biphosphatase (FBP1). In the absence of glucose, C. glabrata shifted its metabolism from glucose catabolism to anabolism of glucose intermediates from the available carbon source. This observation essentially suggests that the glyoxylate cycle and gluconeogenesis are potentially critical for the survival of phagocytosed C. glabrata within the glucose-deficient macrophages. Here, we presented the first global metabolic responses of C. glabrata to alternative carbon source using transcriptomic and proteomic approaches. These findings implicated that reprogramming of the alternative carbon metabolism during glucose deprivation could enhance the survival and persistence of C. glabrata within the host.

中文翻译：

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转录组和蛋白质组分析揭示了醋酸盐生长的人类病原体光滑念珠菌碳代谢的重编程

光滑念珠菌的出现可导致潜在的危及生命的侵袭性念珠菌病，与高发病率和死亡率广泛相关。为了在体内引起疾病，强大且高效的代谢适应对于这种真菌病原体在人类宿主中的生存至关重要。事实上，碳代谢的重新编程被认为对于感染期间葡萄糖剥夺条件下光滑念珠菌的吞噬是必不可少的。在本研究中，利用高通量转录组学和蛋白质组学方法探讨了光滑 C. glabrata 在醋酸盐生长条件下的代谢反应。总共有 1482 个转录本 (26.96%) 和 242 个蛋白质 (24.69%) 显着上调或下调。转录组和蛋白质组数据都表明，光滑念珠菌中替代碳代谢的调节与其他真菌病原体（例如白色念珠菌和新生隐球菌）类似，乙醛酸循环和糖异生中的许多蛋白质和转录物，即异柠檬酸裂合酶（ICL1）上调。 )、苹果酸合酶 (MLS1)、磷酸烯醇丙酮酸羧激酶 (PCK1) 和果糖 1,6-二磷酸酶 (FBP1)。在缺乏葡萄糖的情况下，光滑 C. glabrata 将其代谢从葡萄糖分解代谢转变为来自可用碳源的葡萄糖中间体的合成代谢。这一观察结果本质上表明，乙醛酸循环和糖异生对于葡萄糖缺乏的巨噬细胞中被吞噬的光滑 C. 光滑细胞的生存可能至关重要。在这里，我们使用转录组学和蛋白质组学方法首次展示了光滑 C. glabrata 对替代碳源的整体代谢反应。这些发现表明，葡萄糖剥夺期间替代碳代谢的重新编程可以增强光滑念珠菌在宿主体内的存活和持久性。