ArticlePloS one2011
Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 110 citations in OpenAlex.
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- In vitro long-term exposure to chlorhexidine or triclosan induces cross-resistance against azoles in Nakaseomyces glabratus.Antimicrobial resistance and infection control · 2025Article
- Candida glabrata: A powerhouse of resistance.PLoS pathogens · 2023Article
- Redefining pleiotropic drug resistance in a pathogenic yeast: Pdr1 functions as a sensor of cellular stresses inmSphere · 2023Article
- Antifungal Susceptibility Pattern ofJournal of fungi (Basel, Switzerland) · 2023Article
- Using Bioluminescence to Image Candida glabrata Urinary Tract Infections in Mice.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Characterizing Candida glabrata Pdr1, a Hyperactive Transcription Factor Involved in Azole Resistance.Methods in molecular biology (Clifton, N.J.) · 2023Article
- UsingVirulence · 2022Article
- A novel Candida glabrata doxycycline-inducible system for in vitro/in vivo use.FEMS yeast research · 2022Article
- Intrinsically High Resistance of Candida glabrata to Hydrogen Peroxide and Its Reversal in a Fluconazole-Resistant Mutant.Antimicrobial agents and chemotherapy · 2022Article
- Molecular mechanisms of acquired antifungal drug resistance in principal fungal pathogens and EUCAST guidance for their laboratory detection and clinical implications.The Journal of antimicrobial chemotherapy · 2022Review
- Disclosing azole resistance mechanisms in resistant Candida glabrata strains encoding wild-type or gain-of-function CgPDR1 alleles through comparative genomics and transcriptomics.G3 (Bethesda, Md.) · 2022Article
- The effect of antifungal resistance development on the virulence of Candida species.FEMS yeast research · 2022Article
- Characterization of theJournal of fungi (Basel, Switzerland) · 2022Article
- InvestigatingJournal of fungi (Basel, Switzerland) · 2021Article
- The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.Drugs · 2021Review
- Fluorescent toys 'n' tools lighting the way in fungal research.FEMS microbiology reviews · 2021Article
- Antifungal Drug Resistance: Molecular Mechanisms inChemical reviews · 2021Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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