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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Indole propionic acid induced Ca2+ -dependent apoptosis in Candida albicans
1School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, South Korea.
Abstract:
Indole propionic acid (IPA) which majorly influences the modulation of cellular respiration is a metabolite generated by gut microbiota. The antimicrobial effects of IPA have not been previously demonstrated. Therefore, this study focused on investigating the antimicrobial activity of IPA. Initially, antifungal activity of IPA against Candida albicans was observed, accompanied by variations in mitochondrial respiration indicating modulation of NAD+ /NADH ratios. Consumption of O2 contributes to the respiratory regulation and triggered by Ca2+ overloading. After treatment with IPA, the cells were monitored, and Ca2+ increases leading to membrane depolarization and reactive oxygen species (ROS) accumulation in mitochondria were noted. Depolarization of mitochondria membrane induced release of proapoptotic proteins in mitochondria. Oxidative stress exerted by ROS contributed to glutathione depletion and oxidation of glutathione (GSH). Fragmentation of DNA is a characteristic event leading to apoptosis and accompanies major hallmarks of apoptosis including phosphatidylserine exposure and metacaspase activation. In addition, phosphatidylserine exposure and metacaspase activation were detected in the cell treated with IPA. In conclusion, IPA triggered apoptosis in C. albicans under the influence of Ca2+ .
Insights
Indole propionic acid (IPA), a gut microbe metabolite, demonstrates antifungal properties against Candida albicans. IPA induces apoptosis by disrupting mitochondrial function, increasing reactive oxygen species, and triggering programmed cell death.
Area of Science:
- Microbiology
- Biochemistry
- Cell Biology
Background:
- Indole propionic acid (IPA) is a gut microbiota metabolite primarily involved in cellular respiration.
- The antimicrobial potential of IPA has not been previously established.
- Candida albicans is a significant opportunistic fungal pathogen.
Purpose of the Study:
- To investigate the antimicrobial activity of IPA.
- To elucidate the mechanism of IPA's action against Candida albicans.
Main Methods:
- Antifungal activity assays against Candida albicans.
- Monitoring of mitochondrial respiration and NAD+/NADH ratios.
- Measurement of Ca2+ levels, mitochondrial membrane potential, and ROS production.
- Analysis of proapoptotic protein release, glutathione levels, DNA fragmentation, phosphatidylserine exposure, and metacaspase activation.
Main Results:
- IPA exhibited antifungal activity against Candida albicans.
- IPA treatment modulated mitochondrial respiration, altering NAD+/NADH ratios.
- IPA induced Ca2+ influx, leading to mitochondrial membrane depolarization and ROS accumulation.
- IPA triggered apoptosis in Candida albicans, evidenced by DNA fragmentation, phosphatidylserine exposure, and metacaspase activation.
Conclusions:
- Indole propionic acid effectively inhibits Candida albicans growth.
- IPA induces apoptosis in Candida albicans through calcium-dependent mitochondrial dysfunction and oxidative stress.
- IPA represents a potential therapeutic agent against fungal infections.
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