ArticlePloS one2015
Contribution of Fdh3 and Glr1 to Glutathione Redox State, Stress Adaptation and Virulence in Candida albicans.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
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- A roadmap to chemically reactive species: how diverse oxidants affectMicrobiology and molecular biology reviews : MMBR · 2025Review
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- Candida albicans pathways that protect against organic peroxides and lipid peroxidation.PLoS genetics · 2024Article
- Glucose-enhanced oxidative stress resistance-A protective anticipatory response that enhances the fitness of Candida albicans during systemic infection.PLoS pathogens · 2023Article
- Fungal resilience and host-pathogen interactions: Future perspectives and opportunities.Parasite immunology · 2023Review
- Insight into metabolic sensors of nitrosative stress protection inFrontiers in plant science · 2023Article
- The Role of the Glutathione System in Stress Adaptation, Morphogenesis and Virulence of Pathogenic Fungi.International journal of molecular sciences · 2022Review
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- The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives.FEMS microbiology reviews · 2021Review
- Transcriptional response of Candida albicans to Pseudomonas aeruginosa in a polymicrobial biofilm.G3 (Bethesda, Md.) · 2021Article
- Fungal immunity and pathogenesis in mammals versus the invertebrate model organism Galleria mellonella.Pathogens and disease · 2021Review
- A first insight into the genome of Prototheca wickerhamii, a major causative agent of human protothecosis.BMC genomics · 2021Article
- The critical role ofApplied and environmental microbiology · 2021Article
- The Interactions BetweenFrontiers in microbiology · 2021Review
- Shifts in microbial community, pathogenicity-related genes and antibiotic resistance genes during dairy manure piled up.Microbial biotechnology · 2020Article
- Transcript profiling reveals potential regulators for oxidative stress response of a necrotrophic chickpea pathogen3 Biotech · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The major fungal pathogen of humans, Candida albicans, is exposed to reactive nitrogen and oxygen species following phagocytosis by host immune cells. In response to these toxins, this fungus activates potent anti-stress responses that include scavenging of reactive nitrosative and oxidative species via the glutathione system. Here we examine the differential roles of two glutathione recycling enzymes in redox homeostasis, stress adaptation and virulence in C. albicans: glutathione reductase (Glr1) and the S-nitrosoglutathione reductase (GSNOR), Fdh3. We show that the NADPH-dependent Glr1 recycles GSSG to GSH, is induced in response to oxidative stress and is required for resistance to macrophage killing. GLR1 deletion increases the sensitivity of C. albicans cells to H2O2, but not to formaldehyde or NO. In contrast, Fdh3 detoxifies GSNO to GSSG and NH3, and FDH3 inactivation delays NO adaptation and increases NO sensitivity. C. albicans fdh3⎔ cells are also sensitive to formaldehyde, suggesting that Fdh3 also contributes to formaldehyde detoxification. FDH3 is induced in response to nitrosative, oxidative and formaldehyde stress, and fdh3Δ cells are more sensitive to killing by macrophages. Both Glr1 and Fdh3 contribute to virulence in the Galleria mellonella and mouse models of systemic infection. We conclude that Glr1 and Fdh3 play differential roles during the adaptation of C. albicans cells to oxidative, nitrosative and formaldehyde stress, and hence during the colonisation of the host. Our findings emphasise the importance of the glutathione system and the maintenance of intracellular redox homeostasis in this major pathogen.
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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.