KRE genes are required for β‐1,6‐glucan synthesis, maintenance of capsule architecture and cell wall protein anchoring in Cryptococcus neoformans

Gilbert, Nicole M.; Donlin, Maureen J.; Gerik, Kimberly J.; Specht, Charles A.; Djordjevic, Julianne T.; Wilson, Christabel F.; Sorrell, Tania C.; Lodge, Jennifer K.

doi:10.1111/j.1365-2958.2010.07119.x

Cited by 113Fungal Infections and StudiesFungal and yeast genetics researchAntifungal resistance and susceptibility

KRE genes are required for β‐1,6‐glucan synthesis, maintenance of capsule architecture and cell wall protein anchoring in Cryptococcus neoformans

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Gilbert, Nicole M., Donlin, Maureen J., Gerik, Kimberly J., Specht, Charles A., Djordjevic, Julianne T., Wilson, Christabel F., Sorrell, Tania C., Lodge, Jennifer K.·2010·Molecular Microbiology

DOI 10.1111/j.1365-2958.2010.07119.xPMC PMC2969852

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Abstract

Summary: The polysaccharide β‐1,6‐glucan is a major component of the cell wall of Cryptococcus neoformans , but its function has not been investigated in this fungal pathogen. We have identified and characterized seven genes, belonging to the KRE family, which are putatively involved in β‐1,6‐glucan synthesis. The H99 deletion mutants kre5 Δ and kre6 Δ skn1 Δ contained less cell wall β‐1,6‐glucan, grew slowly with an aberrant morphology, were highly sensitive to environmental and chemical stress and were avirulent in a mouse inhalation model of infection. These two mutants displayed alterations in cell wall chitosan and the exopolysaccharide capsule, a primary cryptococcal virulence determinant. The cell wall content of the GPI‐anchored phospholipase B1 (Plb1) enzyme, which is required for cryptococcal cell wall integrity and virulence, was reduced in kre5 Δ and kre6 Δ skn1 Δ. Our results indicate that KRE5 , KRE6 and SKN1 are involved in β‐1,6‐glucan synthesis, maintenance of cell wall integrity and retention of mannoproteins and known cryptococcal virulence factors in the cell wall of C. neoformans . This study sets the stage for future investigations into the function of this abundant cell wall polymer.

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Genes involved in β-1,6-glucan synthesis, melanin production, chitin synthesis and chitosan synthesis are cell wall-related genes whose deletion reduces virulence.
“This includes genes involved in the synthesis of β-1,6-glucan (such as KRE5, KRE6 and SKN1)61, the protective pigment melanin (such as the laccase gene LAC1)62, chitin in the cell wall (including the chitin synthase gene CHS3 and the regulator protein gene CSR2)63 and chitosan (exemplified by the chitin deacetylase genes CDA1, CDA2 and CDA3)64,65.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [61]

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Authors: Gilbert, N. M., Donlin, M. J., Gerik, K. J., Specht, C. A., Djordjevic, J. T., Wilson, C. F., Sorrell, T. C., & Lodge, J. K.
Affiliations: Saint Louis University (US)
Washington University in St. Louis (US)
University of Massachusetts Chan Medical School (US)
The University of Sydney (AU)
Corresponding author: Lodge, Jennifer K.
ORCID: Gilbert, Nicole M.
Donlin, Maureen J.
Specht, Charles A.
Djordjevic, Julianne T.
Sorrell, Tania C.
Lodge, Jennifer K.
Venue: Molecular Microbiology
Publisher: Wiley
Published: 2010-04
Volume: 76
Issue: 2
Pages: 517-534
ISSN: 0950-382X (ISSN-L)
1365-2958
DOI: 10.1111/j.1365-2958.2010.07119.x
PMC: PMC2969852
OpenAlex: W2048678419
Cited by: 113
References: 69
Citations by year: 2026: 10 · 2025: 5 · 2024: 13 · 2023: 13 · 2022: 5 · 2021: 9 · 2020: 12 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 5 · 2012: 4
FWCI: 3.96
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 5 d)
Locations: Molecular Microbiology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: American Heart Association
National Institutes of Health
National Institute of Allergy and Infectious Diseases (R01 AI50184, R01AI050184, R01AI072195)
Topics: Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Keywords: Cryptococcus neoformans, cell wall integrity, chitosan, mannoproteins, GPI-anchored proteins, virulence, stress sensitivity, cell wall architecture
MeSH terms: Animals, Architecture, Cell Wall, Cryptococcosis, Cryptococcus neoformans, Disease Models, Animal, Fungal Proteins, Maintenance, Polysaccharides, Protein Binding, Virulence, Survival Analysis, Gene Deletion, beta-Glucans, Mice

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KRE genes are required for β‐1,6‐glucan synthesis, maintenance of capsule architecture and cell wall protein anchoring in Cryptococcus neoformans

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