Cited by 38Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Infections and Studies

Blocking β‐1,6‐glucan synthesis by deleting KRE6 and SKN1 attenuates the virulence of Candida albicans

Han, Qi, Wang, Na, Yao, Guangyin, Mu, Chunhua, Wang, Yue, Sang, Jianli·2019·Molecular Microbiology

Abstract

Summary: β‐1,6‐glucan is an important component of the fungal cell wall. The β‐1,6‐glucan synthase gene KRE6 was thought to be essential in the fungal pathogen Candida albicans because it could not be deleted in previous efforts. Also, the role of its homolog SKN1 was unclear because its deletion caused no defects. Here, we report the construction and characterization of kre6 Δ/Δ, skn1 Δ/Δ and kre6 Δ/Δ skn1 Δ/Δ mutants in C. albicans . While deleting KRE6 or SKN1 had no obvious phenotypic consequence, deleting both caused slow growth, cell separation failure, cell wall abnormalities, diminished hyphal growth, poor biofilm formation and loss of virulence in mice. Furthermore, the GPI‐linked cell surface proteins Hwp1 and the invasin Als3 or Ssa1 were not detected in kre6 Δ/Δ skn1 Δ/Δ mutant. In GMM medium, RT‐qPCR and western blotting revealed a constitutive expression of KRE6 and growth conditions‐associated activation of SKN1 . Like many hypha‐specific genes, SKN1 is repressed by Nrg1, but its activation does not involve the transcription factor Efg1. Dysregulation of SKN1 reduces C. albicans ability to damage epithelial and endothelial cells and attenuates its virulence. Given the vital role of β‐1,6‐glucan synthesis in C. albicans physiology and virulence, Kre6 and Skn1 are worthy targets for developing antifungal agents.

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Crossref · 10.1111/mmi.14176

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  • β-1,6-glucan plays a critical role in adaptive remodeling of the Candida cell wall.

    “Deletion of KRE6a, which encodes β−1,6-glucan synthase, reduces echinocandin susceptibility in C. auris, further highlighting β−1,6-glucan’s critical role in adaptive remodeling.”
  • β-1,6-glucan appears to be a key differentiating factor in the responses of C. albicans and C. auris to caspofungin treatment.

    “Thus, β-1,6-glucan, which plays a crucial role in morphogenesis, cell wall integrity, and virulence36,81,82, appears to be a key differentiating factor in the responses of C. albicans and C. auris to caspofungin treatment.”
  • Two contiguous genes with 57% homology to the β-1,6-glucan synthase gene KRE6 of C. albicans were identified in the C. auris B8441 genome.

    “We identified in the C. auris B8441 genome two contiguous genes with 57% homology to the β-1,6-glucan synthase gene KRE6 of C. albicans82.”
  • KRE6 has been considered essential in C. albicans, but recent success in creating a homozygous KRE6 deletion mutant under specific conditions has raised questions about the essentiality of this gene.

    “Similarly, KRE6 has been considered essential in C. albicans, but the recent success in creating a homozygous KRE6 deletion mutant under specific conditions has raised questions about the essentiality of this gene82.”
  • β-1,6-glucan appears to play critical roles in interacting with both mannan and chitin, as suggested by solid-state NMR results, and may exhibit different behaviors between C. albicans and C. auris in response to echinocandins.

    “Another underexplored molecule is β-1,6-glucan36,82, which appears to play critical roles in interacting with both mannan and chitin, as suggested by solid-state NMR results, and may exhibit different behaviors between C. albicans and C. auris in response to echinocandins.”

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Authors
Han, Q., Wang, N., Yao, G., Mu, C., Wang, Y., & Sang, J.
Affiliations
  • Beijing Normal University (CN)
  • Agency for Science, Technology and Research (SG)
Corresponding author
  • Wang, Yue
  • Sang, Jianli
Venue
Molecular Microbiology
Publisher
Wiley
Published
2019-01-08
Volume
111
Issue
3
Pages
604-620
ISSN
  • 0950-382X (ISSN-L)
  • 1365-2958
OpenAlex
W2902680968
Cited by
38
References
8
Citations by year
2026: 4 · 2025: 4 · 2024: 9 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 5 · 2019: 2
FWCI
1.24
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular Microbiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (31470182, 31270113)
  • Agency for Science, Technology and Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
Candida albicans, β-1,6-glucan, fungal virulence, cell wall, hyphal growth, biofilm formation, HWP1, ALS3, Ssa1, neuregulin-1, EFG1, antifungal drug targets, mouse virulence
MeSH terms
Animals, Candida albicans, Candidiasis, Disease Models, Animal, Glucosyltransferases, Virulence, Gene Deletion, Virulence Factors, beta-Glucans, Mice

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