ArticlePloS one2014
Glutathione metabolism in Candida albicans resistant strains to fluconazole and micafungin.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
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- Integrative functional analysis uncovers metabolic differences between Candida species.Communications biology · 2022Article
- The Role of the Glutathione System in Stress Adaptation, Morphogenesis and Virulence of Pathogenic Fungi.International journal of molecular sciences · 2022Review
- Antifungal Activity of Human Cathelicidin LL-37, a Membrane Disrupting Peptide, by Triggering Oxidative Stress and Cell Cycle Arrest inJournal of fungi (Basel, Switzerland) · 2022Article
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- Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.PloS one · 2021Article
- Nine Things Genomics Can Tell Us AboutFrontiers in genetics · 2020Review
- The Transcription Factor Sfp1 Regulates the Oxidative Stress Response inMicroorganisms · 2019Article
- Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells.Biochimica et biophysica acta. General subjects · 2017Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently available therapies for candidiasis are based on antifungal drugs belonging to azole and echinocandin families that interfere with different aspects of fungal metabolism. These drugs, beyond their specific effects, elicit also a cellular stress including an unbalance of redox state that is counteracted not only utilizing antioxidant species but also increasing the outcome export by transporters to detoxify the internal environment. These cellular actions are both based on the cytosolic concentration of reduced glutathione (GSH). In this paper we investigated the effects of two antifungal drugs fluconazole and micafungin on the redox state of the cell in C. albicans to understand if the resistance to these drugs is accompanied by variation of glutathione metabolism. Analyses of resistant strains showed a marked difference in glutathione contents in strains resistant to fluconazole (CO23RFLC) or micafungin (CO23RFK). In CO23RFLC, the total amount of glutathione was more than doubled with respect to CO23RFK thanks to the increased activity of γ-glutamilcysteine synthetase, the key enzyme involved in GSH synthesis. We demonstrated that the GSH increase in CO23RFLC conferred to this strain a clear advantage in counteracting oxidative toxic agents while assignment of other roles, such as a more efficient elimination of the drug from the cell, should be considered more speculative. As far as MCFG resistance is concerned, from our data a role of glutathione metabolism in supporting this condition is not evident. Overall our data indicate that glutathione metabolism is differently affected in the two resistant strains and that glutathione system may play an important role in the global organization of C.albicans cells for resistance to fluconazole. Such scenario may pave the way to hypothesize the use of oxidant drugs or inhibitors able to deplete reduced glutathione level as a novel approach, for counteracting the resistance to this specific antifungal drug.
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