The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
A Chitin Synthase and Its Regulator Protein Are Critical for Chitosan Production and Growth of the Fungal Pathogen Cryptococcus neoformans
Open accessAbstract
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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“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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Metadata
- 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.
- 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
- 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
- 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 › Infectious Diseases › 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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