ArticleEukaryotic cell2011
Calcineurin controls drug tolerance, hyphal growth, and virulence in Candida dubliniensis.
Article in Eukaryotic cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
59 citing papers in PubMed, 106 citations in OpenAlex.
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- Biased Genotype Distributions of Candida albicans Strains Associated with 649 Clinical Vulvovaginal Candidiasis in China.Mycopathologia · 2022Article
- Updating Insights into the Regulatory Mechanisms of Calcineurin-Activated Transcription Factor Crz1 in Pathogenic Fungi.Journal of fungi (Basel, Switzerland) · 2022Review
- A critical role of calcineurin in stress responses, hyphal formation, and virulence of the pathogenic fungus Trichosporon asahii.Scientific reports · 2022Article
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- Genetic analysis of Hsp90 function in Cryptococcus neoformans highlights key roles in stress tolerance and virulence.Genetics · 2022Article
- CRZ1 transcription factor is involved in cell survival, stress tolerance, and virulence in fungi.Journal of biosciences · 2022Review
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- Aequorin as a Useful Calcium-Sensing Reporter inJournal of fungi (Basel, Switzerland) · 2021Article
- Lineage-specific selection and the evolution of virulence in theProceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Effect of Honokiol on Ergosterol Biosynthesis and Vacuole Function inJournal of microbiology and biotechnology · 2020Article
- Combination Therapy to Treat Fungal Biofilm-Based Infections.International journal of molecular sciences · 2020Review
- Calcineurin Regulates Conidiation, Chlamydospore Formation and Virulence inFrontiers in microbiology · 2020Article
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Authors and funding
12 authors at 8 institutions in 3 countries.
Funding
Abstract
Candida dubliniensis is an emerging pathogenic yeast species closely related to Candida albicans and frequently found colonizing or infecting the oral cavities of HIV/AIDS patients. Drug resistance during C. dubliniensis infection is common and constitutes a significant therapeutic challenge. The calcineurin inhibitor FK506 exhibits synergistic fungicidal activity with azoles or echinocandins in the fungal pathogens C. albicans, Cryptococcus neoformans, and Aspergillus fumigatus. In this study, we show that calcineurin is required for cell wall integrity and wild-type tolerance of C. dubliniensis to azoles and echinocandins; hence, these drugs are candidates for combination therapy with calcineurin inhibitors. In contrast to C. albicans, in which the roles of calcineurin and Crz1 in hyphal growth are unclear, here we show that calcineurin and Crz1 play a clearly demonstrable role in hyphal growth in response to nutrient limitation in C. dubliniensis. We further demonstrate that thigmotropism is controlled by Crz1, but not calcineurin, in C. dubliniensis. Similar to C. albicans, C. dubliniensis calcineurin enhances survival in serum. C. dubliniensis calcineurin and crz1/crz1 mutants exhibit attenuated virulence in a murine systemic infection model, likely attributable to defects in cell wall integrity, hyphal growth, and serum survival. Furthermore, we show that C. dubliniensis calcineurin mutants are unable to establish murine ocular infection or form biofilms in a rat denture model. That calcineurin is required for drug tolerance and virulence makes fungus-specific calcineurin inhibitors attractive candidates for combination therapy with azoles or echinocandins against emerging C. dubliniensis infections.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.