Contribution of CgPDR1-Regulated Genes in Enhanced Virulence of Azole-Resistant Candida glabrata
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In Candida glabrata, the transcription factor CgPdr1 is involved in resistance to azole antifungals via upregulation of ATP binding cassette (ABC)-transporter genes including at least CgCDR1, CgCDR2 and CgSNQ2. A high diversity of GOF (gain-of-function) mutations in CgPDR1 exists for the upregulation of ABC-transporters. These mutations enhance C. glabrata virulence in animal models, thus indicating that CgPDR1 might regulate the expression of yet unidentified virulence factors. We hypothesized that CgPdr1-dependent virulence factor(s) should be commonly regulated by all GOF mutations in CgPDR1. As deduced from transcript profiling with microarrays, a high number of genes (up to 385) were differentially regulated by a selected number (7) of GOF mutations expressed in the same genetic background. Surprisingly, the transcriptional profiles resulting from expression of GOF mutations showed minimal overlap in co-regulated genes. Only two genes, CgCDR1 and PUP1 (for PDR1 upregulated and encoding a mitochondrial protein), were commonly upregulated by all tested GOFs. While both genes mediated azole resistance, although to different extents, their deletions in an azole-resistant isolate led to a reduction of virulence and decreased tissue burden as compared to clinical parents. As expected from their role in C. glabrata virulence, the two genes were expressed as well in vitro and in vivo. The individual overexpression of these two genes in a CgPDR1-independent manner could partially restore phenotypes obtained in clinical isolates. These data therefore demonstrate that at least these two CgPDR1-dependent and -upregulated genes contribute to the enhanced virulence of C. glabrata that acquired azole resistance.
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Specific pdr1 mutations in C. glabrata can lead to a gain of fitness through enhanced adhesion and virulence.
“Specific pdr1 mutations in C. glabrata can also lead to a gain of fitness through enhanced adhesion and virulence”
From Genetic Drivers of Multidrug Resistance in Candida glabrata (2016) · cites this paper as Ferrari et al., 2011
In Candida glabrata, transcription factor Pdr1 is involved in resistance to azoles through upregulation of CDR1, CDR2, and SNQ2.
“In C. glabrata, the transcription factor Pdr1 is involved in resistance to azoles through upregulation of CDR1, CDR2, and SNQ2 [91].”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [91]
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- Authors
- Ferrari, S., Sanguinetti, M., Torelli, R., Posteraro, B., & Sanglard, D.
- Affiliations
- University of Lausanne (CH)
- Università Cattolica del Sacro Cuore (IT)
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Sanglard, Dominique
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-03-09
- Volume
- 6
- Issue
- 3
- Pages
- e17589
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3052359
- OpenAlex
- W2091654454
- Cited by
- 110
- References
- 48
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 8 · 2022: 7 · 2021: 7 · 2020: 9 · 2019: 7 · 2018: 10 · 2017: 7 · 2016: 9 · 2015: 7 · 2014: 10 · 2013: 11 · 2012: 9
- FWCI
- 7.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- 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
- Candida glabrata, azole resistance, virulence, gain-of-function mutations, ABC transporters, transcriptional regulation, gene co-regulation, tissue burden, antifungal resistance
- MeSH terms
- Animals, Antifungal Agents, Azoles, Candidiasis, Disease Models, Animal, Female, Fungal Proteins, Genes, Fungal, Mice, Inbred BALB C, Microbial Sensitivity Tests, Mitochondria, Mutation, Transcription, Genetic, Virulence, Colony Count, Microbial, Fluconazole, Gene Expression Regulation, Fungal, Gene Expression Profiling, Drug Resistance, Fungal, Candida glabrata, Mice
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