GWT1 encoding an inositol acyltransferase homolog is required for laccase repression and stress resistance in the basidiomycete Cryptococcus neoformans
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The transcriptional expression of laccase, which has been confirmed to contribute to the virulence of Cryptococcus neoformans, is often repressed by a high concentration of glucose in many fungi, including C. neoformans. The underlying mechanism of the repression remains largely unknown. In this study, we found that a GWT1 gene that encodes a glycosylphosphatidylinositol (GPI) anchor biosynthesis-related protein is required for laccase repression by glucose in the basidiomycete C. neoformans. Disruption of GWT1 with the Agrobacterium tumefaciens-mediated T-DNA random insertional mutagenesis (ATMT) method resulted in constitutive expression of the laccase gene LAC1 and constant melanin formation. The loss of GWT1 also dramatically affected the cell membrane integrity and stress resistance. Our results revealed a GPI-dependent glucose repression mechanism in C. neoformans, and it may be helpful for understanding the virulence of C. neoformans.
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Gwt1 is an important virulence factor and the enzyme responsible for catalysing an early step in glycosylphosphatidylinositol (GPI)-anchor biosynthesis.
“Gwt1, an important virulence factor and the enzyme responsible for catalysing an early step in glycosylphosphatidylinositol (GPI)-anchor biosynthesis96, has also emerged as a promising antifungal target.”
From Treatment strategies for cryptococcal infection: challenges, advances and future outlook (2021) · cites this paper as [96]
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Research works printed but not linked: 1
- Eigenheer RA, Jin Lee Y, Blumwald E, et al. Extracellu- lar glycosylphosphatidylinositol-anchored mannoproteins and proteases of Cryptococcus neoformans. FEMS Yeast Res 2007;7:499-510.
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Treatment strategies for cryptococcal infection: challenges, advances and future outlook
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- Authors
- Zhao, Q., Wei, D., Li, Z., Wang, Y., Zhu, X., & Zhu, X.
- Affiliations
- Nankai University (CN)
- Corresponding author
- Zhu, Xudong
- Venue
- FEMS Yeast Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-09-26
- Volume
- 15
- Issue
- 8
- Pages
- fov086
- ISSN
- 1567-1356 (ISSN-L)
- 1567-1364
- OpenAlex
- W2261669162
- Cited by
- 8
- References
- 33
- Citations by year
- 2026: 3 · 2023: 2 · 2021: 1 · 2018: 2
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEMS Yeast Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31170076, 31170138)
- 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 › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- glucose repression, melanogenesis, glycosylphosphatidylinositol anchor biosynthesis, plasma membrane integrity, stress tolerance, Cryptococcus neoformans, virulence
- MeSH terms
- Acyltransferases, Cryptococcus neoformans, Repressor Proteins, Stress, Physiological, Gene Expression Regulation, Fungal, Mutagenesis, Insertional, Agrobacterium tumefaciens, Laccase, Gene Knockout Techniques
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