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Cited by 45Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in Candida albicans

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Jia, X. M., Wang, Y., Jia, Y., Gao, P. H., Xu, Y. G., Wang, L., Cao, Y. Y., Cao, Y. B. +2 more·2009·Cellular and Molecular Life Sciences
DOI 10.1007/s00018-008-8409-3PMC PMC11131505
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Abstract

The calcineurin pathway has been reported to be essential for the development of azole resistance in Candida albicans. The depletion or ectopic over-expression of RTA2 increased or decreased susceptibility of C. albicans to azoles, respectively. CaCl(2)- induced activation of the calcineurin pathway in wildtype C. albicans promoted resistance to azoles, while the Ca(2+) chelator (EGTA), calcineurin inhibitors (FK506 and cyclosporin A) and the deletion of RTA2 blocked the resistance-promoting effects of CaCl(2). Furthermore, we found that RTA2 was up-regulated in a calcineurin-dependent manner. The depletion of RTA2 also made the cell membrane of C. albicans liable to be destroyed by azoles and RTA2 over-expression attenuated the destroying effects. Finally, the disruption of RTA2 caused an increased accumulation of dihydrosphingosine (DHS), one of the two sphingolipid long-chain bases, by decreasing release of DHS. In conclusion, our findings suggest that RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans.

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Crossref · 10.1007/s00018-008-8409-3

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References 44 · Cited by 45

Authors
Jia, X. M., Wang, Y., Jia, Y., Gao, P. H., Xu, Y. G., Wang, L., Cao, Y. Y., Cao, Y. B., Zhang, L. X., & Jiang, Y. Y.
Affiliations
  • Second Military Medical University (CN)
  • Chinese Academy of Sciences (CN)
Corresponding author
  • Jia, Y.
  • Jiang, Y. Y.
ORCID
Venue
Cellular and Molecular Life Sciences
Publisher
Springer Science and Business Media LLC
Published
2008-11-11
Volume
66
Issue
1
Pages
122-134
ISSN
  • 1420-682X (ISSN-L)
  • 1420-9071
DOI
10.1007/s00018-008-8409-3
PMC
PMC11131505
OpenAlex
W2002753074
Cited by
45
References
44
Citations by year
2026: 1 · 2025: 3 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 9 · 2015: 5 · 2014: 4 · 2013: 2 · 2012: 2
FWCI
0.64
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Cellular and Molecular Life Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
calcineurin pathway, azole resistance, Candida albicans, dihydrosphingosine, sphingolipids, calcium signaling, cell membrane damage, antifungal resistance
MeSH terms
Antifungal Agents, Azoles, Biological Transport, Calcium, Candida albicans, Cell Membrane, Ergosterol, Fungal Proteins, Membrane Proteins, Microbial Sensitivity Tests, Rhodamines, Sphingosine, Up-Regulation, Drug Resistance, Fungal

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