Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
MRC Centre for Medical Mycology, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, EX4 4QD, UK.
J Biomed Sci. 2021 Jan 2;28(1):1. doi: 10.1186/s12929-020-00700-8.
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.
光滑念珠菌的出现与高发病率和死亡率密切相关，它可导致潜在的致命性侵袭性念珠菌病。为了在体内引起疾病，这种真菌病原体在人体宿主中需要强大而高效的代谢适应才能存活。事实上，在感染过程中吞噬的光滑念珠菌在葡萄糖剥夺条件下，人们认为重新编程碳代谢对于其存活是必不可少的。
在这项研究中，使用高通量转录组学和蛋白质组学方法探索了光滑念珠菌在乙酸盐生长条件下的代谢反应。
共有 1482 个转录本（26.96%）和 242 个蛋白质（24.69%）显著上调或下调。转录组和蛋白质组数据均表明，光滑念珠菌中替代碳代谢的调节类似于其他真菌病原体，如白色念珠菌和新型隐球菌，其中许多来自乙醛酸循环和糖异生的蛋白质和转录本上调，即异柠檬酸裂解酶（ICL1）、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）。在没有葡萄糖的情况下，光滑念珠菌将其代谢从葡萄糖分解代谢转变为可用碳源中葡萄糖中间产物的合成代谢。这一观察结果实质上表明，乙醛酸循环和糖异生对于吞噬的光滑念珠菌在葡萄糖缺乏的巨噬细胞中的存活至关重要。
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念珠菌对替代碳源的全局代谢反应。这些发现表明，在葡萄糖剥夺期间重新编程替代碳代谢可以增强光滑念珠菌在宿主中的存活和持久性。
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