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

Shu Yih Chew, Kok Lian Ho, Yoke Kqueen Cheah, Tzu Shan Ng, Doblin Sandai, Alistair J. P. Brown, Leslie Than Thian Lung (Corresponding Author)

Research output: Contribution to journalArticle

4 Citations (Scopus)
3 Downloads (Pure)

Abstract

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.
Original languageEnglish
Article number2843
Pages (from-to)2843
Number of pages11
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 26 Feb 2019

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Candida glabrata
Virulence
Genes
Carbon
Macrophages
Invasive Candidiasis
glyoxylic acid
Oleic Acid
Biofilms
Growth
Acetates
Ethanol
Glucose
Survival

Keywords

  • ALBICANS
  • ASPERGILLUS-FUMIGATUS
  • CARBON UTILIZATION
  • ISOCITRATE LYASE
  • MACROPHAGE
  • PATHWAYS
  • SURVIVAL

ASJC Scopus subject areas

  • General

Cite this

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.; Lung, Leslie Than Thian (Corresponding Author).

In: Scientific Reports, Vol. 9, No. 1, 2843, 26.02.2019, p. 2843.

Research output: Contribution to journalArticle

Chew, Shu Yih ; Ho, Kok Lian ; Cheah, Yoke Kqueen ; Ng, Tzu Shan ; Sandai, Doblin ; Brown, Alistair J. P. ; Lung, Leslie Than Thian. / Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata. In: Scientific Reports. 2019 ; Vol. 9, No. 1. pp. 2843.
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abstract = "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.",
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note = "We would like to acknowledge Professor Karl Kuchler from Medical University of Vienna for the kind gifts of C. glabrata strains used in this study. This study was funded by Fundamental Research Grant Scheme (FRGS) from Ministry of Education (MOE), Malaysia (Grant number: 01-01-14-1456FR). S.Y. is a recipient of the MyBrain 15 Scholarship from MOE, Malaysia. A.B. was supported by the Medical Research Council Centre for Medical Mycology at the University of Aberdeen (MR/N006364/1), by a programme grant from the UK Medical Research Council (MR/M026663/1), by a Strategic Award from the Wellcome Trust (097377) and by a grant from the UK Biotechnology and Biological Sciences Research Council (BB/P020119/1).",
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N2 - 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.

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