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Fungistatic Effect of Phthalide Lactones on Rhodotorula mucilaginosa
Joanna Gach1, Teresa Olejniczak1, Jakub Pannek1
1Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland.
Abstract:
Currently, there is an increasing number of cases of fungal infections caused by opportunistic strains of the yeast Rhodotorula mucilaginosa, mainly in immunocompromised patients during hospitalization. The excessive use of antibiotics and azole compounds increases the risk of resistance to microorganisms. A new alternative to these drugs may be synthetic phthalide lactones with a structure identical to or similar to the natural ones found in celery plants, which show low toxicity and relatively high fungistatic activity. In the present study, the fungistatic activity of seven phthalide lactones was determined against R. mucilaginosa IHEM 18459. We showed that 3-n-butylidenephthalide, the most potent compound selected in the microdilution test, caused a dose-dependent decrease in dry yeast biomass. Phthalide accumulated in yeast cells and contributed to an increase in reactive oxygen species content. The synergistic effect of fluconazole resulted in a reduction in the azole concentration required for yeast inhibition. We observed changes in the color of the yeast cultures; thus, we conducted experiments to prove that the carotenoid profile was altered. The addition of lactones also triggered a decline in fatty acid methyl esters.
Insights
New synthetic phthalide lactones show promise in combating drug-resistant fungal infections like Rhodotorula mucilaginosa. These compounds, derived from celery, reduce yeast growth and enhance antifungal drug effectiveness.
Area of Science:
- Mycology
- Medicinal Chemistry
Background:
- Rising incidence of opportunistic fungal infections, particularly Rhodotorula mucilaginosa, in immunocompromised patients.
- Increasing antimicrobial resistance to antibiotics and azoles necessitates novel therapeutic strategies.
- Synthetic phthalide lactones, inspired by natural compounds, offer a potential low-toxicity alternative with fungistatic properties.
Purpose of the Study:
- To evaluate the fungistatic activity of seven synthetic phthalide lactones against Rhodotorula mucilaginosa.
- To investigate the mechanism of action of the most potent phthalide lactone.
- To assess the synergistic effect of phthalide lactones with fluconazole.
Main Methods:
- Microdilution assays to determine fungistatic activity.
- Measurement of yeast biomass, reactive oxygen species (ROS) content, and carotenoid profiles.
- Analysis of fatty acid methyl esters.
- Synergy testing with fluconazole.
Main Results:
- 3-n-butylidenephthalide demonstrated significant dose-dependent inhibition of R. mucilaginosa growth.
- Phthalide accumulation in yeast cells led to increased ROS production.
- Synergistic effects were observed between phthalide lactones and fluconazole, reducing required azole concentrations.
- Alterations in yeast carotenoid profiles and a decline in fatty acid methyl esters were noted.
Conclusions:
- Synthetic phthalide lactones exhibit potent fungistatic activity against Rhodotorula mucilaginosa.
- The mechanism involves intracellular accumulation, ROS induction, and potential disruption of cellular components.
- Phthalide lactones can potentiate the efficacy of existing antifungal agents like fluconazole, offering a strategy to overcome resistance.
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