Differential cell wall remodeling of two chitin synthase deletants Δchs3A and Δchs3B in the pathogenic yeast Candida glabrata: Cell wall remodeling of Δchs3 mutants
Open accessAbstract
It is known that cell wall remodeling and the salvaging pathway act to compensate for an impaired or a damaged cell wall. Lately, it has been indicated that this mechanism is partly required for resistance to the glucan synthesis inhibitor echinocandin. While cell wall remodeling has been described in mutants of glucan or mannan synthesis, it has not yet been reported in a chitin synthesis mutant. Here, we describe a novel cell wall remodeling and salvaging pathway in chitin synthesis mutants, Δchs3A and Δchs3B, of the pathogenic yeast Candida glabrata. Electron microscopic analysis revealed a thickened mannoprotein layer in Δchs3A cells and a thickened chitin-glucan layer of Δchs3B cells, and it indicated the hypothesis that mannan synthase and chitin-glucan synthase indemnify Δchs3A and Δchs3B cells, respectively. The double-mutant CHS3A and MNN10, encoding α-1,6-mannosyltransferase, showed synergistic stress sensitization, and the Δchs3B strain showed supersensitivity to echinocandins. Hence, these findings support the above hypothesis of remodeling. Furthermore, unlike Δchs3A cells, Δchs3B cells showed supersensitivity to calcineurin inhibitor FK506 and Tor1p kinase inhibitor rapamycin, indicating that the Δchs3B strain uses the calcineurin pathway and a Tor1p kinase for cell wall remodeling.
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Genetic or chemical targeting of chitin synthase increases C. glabrata susceptibility to echinocandins in vitro.
“Genetic (Ueno et al., 2011; Schwarzmuller et al., 2014) or chemical (Miyazaki et al., 2010a) targeting of chitin synthase has been shown to increase C. glabrata susceptibility to echinocandins in vitro.”
From Genetic Drivers of Multidrug Resistance in Candida glabrata (2016) · cites this paper as Ueno et al., 2011
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Genetic Drivers of Multidrug Resistance in Candida glabrata
Healey, K. R., Jimenez Ortigosa, C., Shor, E., & Perlin, D. S. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01995 · Cited by 93 · see citing works
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- Authors
- Ueno, K., Namiki, Y., Mitani, H., Yamaguchi, M., & Chibana, H.
- Affiliations
- Chiba University (JP)
- Corresponding author
- Chibana, Hiroji
- Venue
- FEMS Yeast Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-04-26
- Volume
- 11
- Issue
- 5
- Pages
- 398-407
- ISSN
- 1567-1356 (ISSN-L)
- OpenAlex
- W1951893039
- Cited by
- 17
- References
- 62
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 5 · 2014: 1 · 2013: 1
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEMS Yeast Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Otago
- Ministry of Education, Culture, Sports, Science and Technology
- 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 glabrata, chitin synthase, cell wall remodeling, calcineurin pathway, rapamycin, FK506, stress sensitization
- MeSH terms
- Amino Acid Sequence, Aminoglycosides, Cell Wall, Chitin, Chitin Synthase, Fungal Proteins, Glucans, Mannans, Membrane Glycoproteins, Stress, Physiological, Signal Transduction, Sequence Alignment, Sequence Deletion, Calcineurin, Candida glabrata, Echinocandins
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