A Chitin Synthase and Its Regulator Protein Are Critical for Chitosan Production and Growth of the Fungal Pathogen Cryptococcus neoformans

Banks, Isaac R.; Specht, Charles A.; Donlin, Maureen J.; Gerik, Kimberly J.; Levitz, Stuart M.; Lodge, Jennifer K.

doi:10.1128/ec.4.11.1902-1912.2005

Cited by 245Fungal and yeast genetics researchFungal Infections and StudiesStudies on Chitinases and Chitosanases

A Chitin Synthase and Its Regulator Protein Are Critical for Chitosan Production and Growth of the Fungal Pathogen Cryptococcus neoformans

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Banks, Isaac R., Specht, Charles A., Donlin, Maureen J., Gerik, Kimberly J., Levitz, Stuart M., Lodge, Jennifer K.·2005·Eukaryotic Cell

DOI 10.1128/ec.4.11.1902-1912.2005PMC PMC1287864

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Abstract

Chitin is an essential component of the cell wall of many fungi. Chitin also can be enzymatically deacetylated to chitosan, a more flexible and soluble polymer. Cryptococcus neoformans is a fungal pathogen that causes cryptococcal meningoencephalitis, particularly in immunocompromised patients. In this work, we show that both chitin and chitosan are present in the cell wall of vegetatively growing C. neoformans yeast cells and that the levels of both rise dramatically as cells grow to higher density in liquid culture. C. neoformans has eight putative chitin synthases, and strains with any one chitin synthase deleted are viable at 30°C. In addition, C. neoformans genes encode three putative regulator proteins, which are homologs of Saccharomyces cerevisiae Skt5p. None of these three is essential for viability. However, one of the chitin synthases (Chs3) and one of the regulators (Csr2) are important for growth. Cells with deletions in either CHS3 or CSR2 have several shared phenotypes, including sensitivity to growth at 37°C. The similarity of their phenotypes also suggests that Csr2 specifically regulates chitin synthesis by Chs3. Lastly, both chs3Δ and the csr2Δ mutants are defective in chitosan production, predicting that Chs3-Csr2 complex with chitin deacetylases for conversion of chitin to chitosan. These data suggest that chitin synthesis could be an excellent antifungal target.

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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 [63]

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Cryptococcal meningitis
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Posttranslational, Translational, and Transcriptional Responses to Nitric Oxide Stress in Cryptococcus neoformans : Implications for Virulence
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Insights into nanomycoremediation: Secretomics and mycogenic biopolymer nanocomposites for heavy metal detoxification
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Cryptococcus neoformans Infection in the Central Nervous System: The Battle between Host and Pathogen
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Chitosan Mediates Germling Adhesion in Magnaporthe oryzae and Is Required for Surface Sensing and Germling Morphogenesis
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Role for Chitin and Chitooligomers in the Capsular Architecture of Cryptococcus neoformans
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Cryptococcus neoformans Chitin Synthase 3 Plays a Critical Role in Dampening Host Inflammatory Responses
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Cross Talk between the Cell Wall Integrity and Cyclic AMP/Protein Kinase A Pathways in Cryptococcus neoformans
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N-acetylglucosamine affects Cryptococcus neoformans cell-wall composition and melanin architecture
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Cryptococcus: History, Epidemiology and Immune Evasion
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Cryptococcus neoformans Cda1 and Cda2 coordinate deacetylation of chitin during infection to control fungal virulence
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Comparative characterization of putative chitin deacetylases from Phaeodactylum tricornutum and Thalassiosira pseudonana highlights the potential for distinct chitin‐based metabolic processes in diatoms
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Self-citation

Authors: Banks, I. R., Specht, C. A., Donlin, M. J., Gerik, K. J., Levitz, S. M., & Lodge, J. K.
Affiliations: Edward A. Doisy Department of Biochemistry and Molecular Biology
Boston University (US)
Saint Louis University (US)
Corresponding author: Banks, Isaac R.
ORCID: Specht, Charles A.
Donlin, Maureen J.
Levitz, Stuart M.
Lodge, Jennifer K.
Venue: Eukaryotic Cell
Publisher: American Society for Microbiology
Published: 2005-11
Volume: 4
Issue: 11
Pages: 1902-1912
ISSN: 1535-9778 (ISSN-L)
1535-9786
DOI: 10.1128/ec.4.11.1902-1912.2005
PMC: PMC1287864
OpenAlex: W2152995920
Cited by: 245
References: 64
Citations by year: 2026: 15 · 2025: 12 · 2024: 19 · 2023: 13 · 2022: 15 · 2021: 12 · 2020: 18 · 2019: 15 · 2018: 13 · 2017: 13 · 2016: 10 · 2015: 12 · 2014: 9 · 2013: 9 · 2012: 8
FWCI: 3.02
Type: journal article
Language: en
Open access: diamond
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Eukaryotic Cell (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: University of Oklahoma
Broad Institute
National Institutes of Health (5u01ai047087-03, 5u01ai048594-02)
National Institute of Allergy and Infectious Diseases (R01 AI50184, U01 AI48594, R01AI050184, R01AI025780, U01AI47087, AI147079)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Studies on Chitinases and Chitosanases
Keywords: Cryptococcus neoformans, chitin synthase, chitosan production, chitin deacetylation, chitin deacetylase, CHS3, fungal cell wall, fungal growth regulation, antifungal drug targets, cryptococcal meningoencephalitis
MeSH terms: Cell Wall, Chitin, Chitin Synthase, Cryptococcus neoformans, Fungal Proteins, Genes, Fungal, Humans, Melanins, Molecular Sequence Data, Gene Expression Regulation, Fungal, Chitosan, Cell Shape

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A Chitin Synthase and Its Regulator Protein Are Critical for Chitosan Production and Growth of the Fungal Pathogen Cryptococcus neoformans

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