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Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata

The human fungal pathogen Candida glabrata appears to utilise unique stealth, evasion and persistence strategies in subverting the onslaught of host immune response during systemic infection. However, macrophages actively deprive the intracellular fungal pathogen of glucose, and therefore alternativ...

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Main Authors: Chew, Shu Yih, Ho, Kok Lian, Cheah, Yoke Kqueen, Ng, Tzu Shan, Sandai, Doblin, Brown, Alistair J. P., Than, Leslie Thian Lung
Format: Article
Published: Nature Publishing Group 2019
Online Access:http://psasir.upm.edu.my/id/eprint/80001/
https://www.nature.com/articles/s41598-019-39117-1#:~:text=In%20conclusion%2C%20a%20functional%20glyoxylate,potential%20for%20future%20therapeutic%20intervention.
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spelling my.upm.eprints.800012023-05-30T08:57:43Z http://psasir.upm.edu.my/id/eprint/80001/ Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata Chew, Shu Yih Ho, Kok Lian Cheah, Yoke Kqueen Ng, Tzu Shan Sandai, Doblin Brown, Alistair J. P. Than, Leslie Thian Lung The human fungal pathogen Candida glabrata appears to utilise unique stealth, evasion and persistence strategies in subverting the onslaught of host immune response during systemic infection. However, macrophages actively deprive the intracellular fungal pathogen of glucose, and therefore alternative carbon sources probably support the growth and survival of engulfed C. glabrata. The present study aimed to investigate the role of the glyoxylate cycle gene ICL1 in alternative carbon utilisation and its importance for the virulence of C. glabrata. The data showed that disruption of ICL1 rendered C. glabrata unable to utilise acetate, ethanol or oleic acid. In addition, C. glabrata icl1∆ cells displayed significantly reduced biofilm growth in the presence of several alternative carbon sources. It was also found that ICL1 is crucial for the survival of C. glabrata in response to macrophage engulfment. Disruption of ICL1 also conferred a severe attenuation in the virulence of C. glabrata in the mouse model of invasive candidiasis. In conclusion, a functional glyoxylate cycle is essential for C. glabrata to utilise certain alternative carbon sources in vitro and to display full virulence in vivo. This reinforces the view that antifungal drugs that target fungal Icl1 have potential for future therapeutic intervention. Nature Publishing Group 2019 Article PeerReviewed Chew, Shu Yih and Ho, Kok Lian and Cheah, Yoke Kqueen and Ng, Tzu Shan and Sandai, Doblin and Brown, Alistair J. P. and Than, Leslie Thian Lung (2019) Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata. Scientific Reports, 9. art. no. 2843. pp. 1-11. ISSN 2045-2322 https://www.nature.com/articles/s41598-019-39117-1#:~:text=In%20conclusion%2C%20a%20functional%20glyoxylate,potential%20for%20future%20therapeutic%20intervention. 10.1038/s41598-019-39117-1
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
description The human fungal pathogen Candida glabrata appears to utilise unique stealth, evasion and persistence strategies in subverting the onslaught of host immune response during systemic infection. However, macrophages actively deprive the intracellular fungal pathogen of glucose, and therefore alternative carbon sources probably support the growth and survival of engulfed C. glabrata. The present study aimed to investigate the role of the glyoxylate cycle gene ICL1 in alternative carbon utilisation and its importance for the virulence of C. glabrata. The data showed that disruption of ICL1 rendered C. glabrata unable to utilise acetate, ethanol or oleic acid. In addition, C. glabrata icl1∆ cells displayed significantly reduced biofilm growth in the presence of several alternative carbon sources. It was also found that ICL1 is crucial for the survival of C. glabrata in response to macrophage engulfment. Disruption of ICL1 also conferred a severe attenuation in the virulence of C. glabrata in the mouse model of invasive candidiasis. In conclusion, a functional glyoxylate cycle is essential for C. glabrata to utilise certain alternative carbon sources in vitro and to display full virulence in vivo. This reinforces the view that antifungal drugs that target fungal Icl1 have potential for future therapeutic intervention.
format Article
author Chew, Shu Yih
Ho, Kok Lian
Cheah, Yoke Kqueen
Ng, Tzu Shan
Sandai, Doblin
Brown, Alistair J. P.
Than, Leslie Thian Lung
spellingShingle Chew, Shu Yih
Ho, Kok Lian
Cheah, Yoke Kqueen
Ng, Tzu Shan
Sandai, Doblin
Brown, Alistair J. P.
Than, Leslie Thian Lung
Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata
author_facet Chew, Shu Yih
Ho, Kok Lian
Cheah, Yoke Kqueen
Ng, Tzu Shan
Sandai, Doblin
Brown, Alistair J. P.
Than, Leslie Thian Lung
author_sort Chew, Shu Yih
title Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata
title_short Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata
title_full Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata
title_fullStr Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata
title_full_unstemmed Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata
title_sort glyoxylate cycle gene icl1 is essential for the metabolic flexibility and virulence of candida glabrata
publisher Nature Publishing Group
publishDate 2019
url http://psasir.upm.edu.my/id/eprint/80001/
https://www.nature.com/articles/s41598-019-39117-1#:~:text=In%20conclusion%2C%20a%20functional%20glyoxylate,potential%20for%20future%20therapeutic%20intervention.
_version_ 1768009362460114944
score 13.211869

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