Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata

Background: 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 path...

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Main Authors: Chew, Shu Yih, Brown, Alistair J. P., Lau, Benjamin Yii Chung, Cheah, Yoke Kqueen, Ho, Kok Lian, Sandai, Doblin, Yahaya, Hassan, Than, Leslie Thian Lung
Format: Article
Published: BMC 2021
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author Chew, Shu Yih
Brown, Alistair J. P.
Lau, Benjamin Yii Chung
Cheah, Yoke Kqueen
Ho, Kok Lian
Sandai, Doblin
Yahaya, Hassan
Than, Leslie Thian Lung
author_facet Chew, Shu Yih
Brown, Alistair J. P.
Lau, Benjamin Yii Chung
Cheah, Yoke Kqueen
Ho, Kok Lian
Sandai, Doblin
Yahaya, Hassan
Than, Leslie Thian Lung
author_sort Chew, Shu Yih
collection UPM
description Background: 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. Methods: In this study, the metabolic responses of C. glabrata under acetate growth condition was explored using high-throughput transcriptomic and proteomic approaches. Results: 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. Conclusion: 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.
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spelling upm.eprints-934152023-01-12T04:51:27Z http://psasir.upm.edu.my/id/eprint/93415/ Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata Chew, Shu Yih Brown, Alistair J. P. Lau, Benjamin Yii Chung Cheah, Yoke Kqueen Ho, Kok Lian Sandai, Doblin Yahaya, Hassan Than, Leslie Thian Lung Background: 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. Methods: In this study, the metabolic responses of C. glabrata under acetate growth condition was explored using high-throughput transcriptomic and proteomic approaches. Results: 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. Conclusion: 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. BMC 2021-01-02 Article PeerReviewed Chew, Shu Yih and Brown, Alistair J. P. and Lau, Benjamin Yii Chung and Cheah, Yoke Kqueen and Ho, Kok Lian and Sandai, Doblin and Yahaya, Hassan and Than, Leslie Thian Lung (2021) Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata. Journal of Biomedical Science, 28 (1). Jan-17. ISSN 1423-0127 https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-020-00700-8 10.1186/s12929-020-00700-8
spellingShingle Chew, Shu Yih
Brown, Alistair J. P.
Lau, Benjamin Yii Chung
Cheah, Yoke Kqueen
Ho, Kok Lian
Sandai, Doblin
Yahaya, Hassan
Than, Leslie Thian Lung
Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata
title Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata
title_full Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata
title_fullStr Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata
title_full_unstemmed Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata
title_short Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata
title_sort transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate grown human pathogen candida glabrata
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