Cited by 49Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

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

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Chew, Shu Yih, Ho, Kok Lian, Cheah, Yoke Kqueen, Ng, Tzu Shan, Sandai, Doblin, Brown, Alistair J. P., Than, Leslie Thian Lung·2019·Scientific Reports

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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Authors
Chew, S. Y., Ho, K. L., Cheah, Y. K., Ng, T. S., Sandai, D., Brown, A. J. P., & Than, L. T. L.
Affiliations
  • Universiti Putra Malaysia (MY)
  • University of Malaya (MY)
  • Universiti Sains Malaysia (MY)
  • University of Aberdeen (GB)
Corresponding author
Than, Leslie Thian Lung
Venue
Scientific Reports
Published
2019-02-26
Volume
9
Issue
1
Pages
2843-2843
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2939738000
Cited by
49
References
43
Citations by year
2026: 7 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 1 · 2021: 6 · 2020: 9 · 2019: 5
FWCI
4.03
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Universiti Putra Malaysia Institutional Repository (Universiti Putra Malaysia) (acceptedVersion)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Greater South Information System
Funders
Ministry of Education
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
Candida glabrata, glyoxylate cycle, alternative carbon sources, metabolic flexibility, fungal virulence, invasive candidiasis, macrophage engulfment, biofilm formation, antifungal drug targets
MeSH terms
RAW 264.7 Cells, Ethanol, Animals, Candidiasis, Disease Models, Animal, Female, Fungal Proteins, Isocitrate Lyase, Macrophages, Virulence, Oleic Acid, Acetic Acid, Candida glabrata, Mice

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