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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Calcium and oxidative stress mediate perillaldehyde-induced apoptosis in Candida albicans
Hui Tian1, Su Qu1, Yanzhen Wang1
1College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.
Abstract:
New anti-Candida albicans drugs are needed due to the emergence of resistant cases in recent years. Perillaldehyde (PAE) is a natural monoterpenoid compound derived from Perilla frutescens. The minimum inhibitory concentration of PAE against C. albicans was 0.4 μL/mL. We aimed to elucidate the antifungal mode of action of PAE against C. albicans. The antifungal activity of PAE against C. albicans was found to correlate with an elevation in intracellular Ca2+ and accumulation of ROS. Several downstream apoptosis events such as the disruption of mitochondrial membrane potential, phosphatidylserine externalization, cytochrome c release, and metacaspase activation were observed in PAE-treated cells. DNA damage and nuclear fragmentation assays also revealed apoptosis of C. albicans cells. In summary, by means of fluorescent microscopy, flow cytometer analysis, and Western blot, our data uncovered that PAE exerts its antifungal activity through Ca2+ and oxidative stress-mediated apoptosis mechanisms. This study deciphered the mode of action of PAE, which will be useful in the design of improved antifungal therapies.
Insights
New research reveals perillaldehyde (PAE) fights Candida albicans by inducing calcium influx and oxidative stress, leading to fungal cell apoptosis. This discovery offers a new strategy for developing antifungal drugs against resistant strains.
Area of Science:
- Mycology
- Pharmacology
- Biochemistry
Background:
- Emergence of drug-resistant Candida albicans necessitates novel antifungal agents.
- Perillaldehyde (PAE), a natural monoterpenoid from Perilla frutescens, shows potential antifungal activity.
Purpose of the Study:
- To elucidate the specific antifungal mechanism of perillaldehyde (PAE) against Candida albicans.
- To investigate the molecular pathways targeted by PAE in C. albicans.
Main Methods:
- Minimum inhibitory concentration (MIC) determination for PAE against C. albicans.
- Assessment of intracellular calcium (Ca2+) levels and reactive oxygen species (ROS) accumulation.
- Analysis of apoptosis markers including mitochondrial membrane potential, phosphatidylserine externalization, cytochrome c release, and metacaspase activation.
- Fluorescent microscopy, flow cytometry, and Western blot analysis were employed.
Main Results:
- PAE demonstrated antifungal activity against C. albicans with an MIC of 0.4 μL/mL.
- PAE treatment led to increased intracellular Ca2+ and ROS accumulation in C. albicans.
- Observed downstream apoptosis events included disrupted mitochondrial membrane potential, phosphatidylserine externalization, cytochrome c release, and metacaspase activation.
- DNA damage and nuclear fragmentation confirmed PAE-induced apoptosis.
Conclusions:
- PAE exerts its antifungal effect against Candida albicans via a mechanism involving Ca2+ influx and oxidative stress.
- These cellular events trigger apoptosis, leading to the death of C. albicans cells.
- Understanding PAE's mode of action provides a basis for developing new antifungal therapies.

