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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Melittin triggers apoptosis in Candida albicans through the reactive oxygen species-mediated
1School of Life Sciences, KNU Creative BioResearch Group (BK21 Plus Program), College of Natural Sciences, Kyungpook National University, Daegu, Korea.
Abstract:
Melittin is one of the best-studied antimicrobial peptides, and many studies have focused on the membrane underlying its membrane-disruptive activity. We previously showed that melittin could cause some hallmarks of apoptosis in Candida albicans. Here, we first report the exact mechanism of melittin-induced fungal apoptosis. We first characterized the reactive oxygen species generated by melittin. The results showed that melittin strongly produced highly reactive hydroxyl radicals (˙OH), which contribute to cell death. Next, we showed that melittin also disrupted the mitochondrial membrane potential (ΔΨm) and induced the Ca(2+) release from the endoplasmic reticulum and its remarkable accumulation in mitochondria. Finally, we investigated the role of caspase in the apoptotic pathway. The results showed that melittin activated metacaspase, which was mediated by cytochrome c release. To summarize, melittin is involved in the mitochondria- and caspase-dependent apoptotic pathway in C. albicans. Our findings suggest that melittin possesses a dual antimicrobial mechanism, including membrane-disruptive and apoptotic actions.
Insights
Melittin triggers fungal apoptosis in Candida albicans by generating hydroxyl radicals and disrupting mitochondria. This peptide activates a caspase-dependent pathway, revealing a dual antimicrobial mechanism.
Area of Science:
- Mycology
- Biochemistry
- Cell Biology
Background:
- Melittin, a well-researched antimicrobial peptide, is known for its membrane-disruptive properties.
- Previous studies indicated melittin induces apoptosis hallmarks in Candida albicans.
- The precise mechanism of melittin-induced fungal apoptosis remained unelucidated.
Purpose of the Study:
- To elucidate the exact mechanism of melittin-induced apoptosis in Candida albicans.
- To characterize reactive oxygen species (ROS) production by melittin.
- To investigate melittin's effects on mitochondrial membrane potential, calcium release, and caspase activation.
Main Methods:
- Characterization of reactive oxygen species (ROS) generated by melittin.
- Assessment of mitochondrial membrane potential (ΔΨm) disruption.
- Measurement of Ca(2+) release from the endoplasmic reticulum and mitochondrial accumulation.
- Investigation of metacaspase activation and cytochrome c release.
Main Results:
- Melittin strongly produced hydroxyl radicals (˙OH), contributing to cell death.
- Melittin disrupted mitochondrial membrane potential (ΔΨm).
- Melittin induced Ca(2+) release from the endoplasmic reticulum and its accumulation in mitochondria, activating metacaspase via cytochrome c release.
Conclusions:
- Melittin induces apoptosis in Candida albicans through a mitochondria- and caspase-dependent pathway.
- Melittin exhibits a dual antimicrobial action, combining membrane disruption with apoptosis induction.
- These findings highlight melittin as a potent agent against fungal infections.
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