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The Light-activated Effect of Natural Anthraquinone Parietin against Candida auris and Other Fungal Priority
Johannes Fiala1, Thomas Roach2, Andreas Holzinger2
1Department of Pharmacognosy, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria.
Abstract:
Antimicrobial photodynamic therapy (aPDT) is an evolving treatment strategy against human pathogenic microbes such as the Candida species, including the emerging pathogen C. auris. Using a modified EUCAST protocol, the light-enhanced antifungal activity of the natural compound parietin was explored. The photoactivity was evaluated against three separate strains of five yeasts, and its molecular mode of action was analysed via several techniques, i.e., cellular uptake, reactive electrophilic species (RES), and singlet oxygen yield. Under experimental conditions (λ = 428 nm, H = 30 J/cm2, PI = 30 min), microbial growth was inhibited by more than 90% at parietin concentrations as low as c = 0.156 mg/L (0.55 µM) for C. tropicalis and Cryptococcus neoformans, c = 0.313 mg/L (1.10 µM) for C. auris, c = 0.625 mg/L (2.20 µM) for C. glabrata, and c = 1.250 mg/L (4.40 µM) for C. albicans. Mode-of-action analysis demonstrated fungicidal activity. Parietin targets the cell membrane and induces cell death via ROS-mediated lipid peroxidation after light irradiation. In summary, parietin exhibits light-enhanced fungicidal activity against all Candida species tested (including C. auris) and Cryptococcus neoformans, covering three of the four critical threats on the WHO's most recent fungal priority list.
Insights
Parietin, a natural compound, shows potent antimicrobial photodynamic therapy (aPDT) activity against Candida species and Cryptococcus neoformans. This light-enhanced treatment effectively inhibits fungal growth by targeting cell membranes and inducing cell death.
Area of Science:
- Microbiology
- Photochemistry
- Pharmacology
Background:
- Antimicrobial photodynamic therapy (aPDT) is an emerging strategy for combating pathogenic microbes.
- Candida species, including the critical pathogen Candida auris, pose significant threats to human health.
- Natural compounds are being investigated as novel agents for aPDT.
Purpose of the Study:
- To evaluate the light-enhanced antifungal activity of the natural compound parietin against various yeast species.
- To determine the molecular mechanisms underlying parietin's antifungal action in aPDT.
- To assess parietin's efficacy against WHO priority fungal pathogens.
Main Methods:
- A modified EUCAST protocol was employed to assess parietin's photoactivity.
- Antifungal efficacy was tested against multiple strains of five yeast species.
- Mechanisms of action were investigated through cellular uptake, reactive electrophilic species (RES) analysis, and singlet oxygen yield measurements.
Main Results:
- Parietin demonstrated significant inhibition of microbial growth (>90%) at low concentrations (0.156–1.250 mg/L) under specific light conditions (428 nm, 30 J/cm², 30 min).
- Effective inhibition was observed against Candida tropicalis, Cryptococcus neoformans, Candida auris, Candida glabrata, and Candida albicans.
- Mode-of-action analysis revealed that parietin targets the cell membrane, inducing cell death via ROS-mediated lipid peroxidation upon light irradiation.
Conclusions:
- Parietin exhibits potent light-enhanced fungicidal activity against clinically relevant Candida species and Cryptococcus neoformans.
- Parietin effectively targets three of the four critical fungal threats identified by the WHO.
- Parietin represents a promising natural compound for developing novel aPDT strategies against multidrug-resistant fungi.
