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Published on: December 5, 2020
Disruption of Membrane Integrity by the Bacterium-Derived Antifungal Jagaricin
Daniel Fischer1, Guido Gessner2, Taicia Pacheco Fill3
1Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena, Germany.
Abstract:
Jagaricin is a lipopeptide produced by the bacterial mushroom pathogen Janthinobacterium agaricidamnosum, the causative agent of mushroom soft rot disease. Apart from causing lesions in mushrooms, jagaricin is a potent antifungal active against human-pathogenic fungi. We show that jagaricin acts by impairing membrane integrity, resulting in a rapid flux of ions, including Ca2+, into susceptible target cells. Accordingly, the calcineurin pathway is required for jagaricin tolerance in the fungal pathogen Candida albicans Transcriptional profiling of pathogenic yeasts further revealed that jagaricin triggers cell wall strengthening, general shutdown of membrane potential-driven transport, and the upregulation of lipid transporters, linking cell envelope integrity to jagaricin action and resistance. Whereas jagaricin shows hemolytic effects, it exhibited either no or low plant toxicity at concentrations at which the growth of prevalent phytopathogenic fungi is inhibited. Therefore, jagaricin may have potential for agricultural applications. The action of jagaricin as a membrane-disrupting antifungal is promising but would require modifications for use in humans.
Insights
Jagaricin, a mushroom pathogen-derived lipopeptide, disrupts fungal cell membranes, offering potential agricultural antifungal applications. Further research is needed for human therapeutic use due to hemolytic effects.
Area of Science:
- Microbiology
- Mycology
- Biochemistry
Background:
- Jagaricin is a lipopeptide produced by *Janthinobacterium agaricidamnosum*, a bacterial pathogen causing mushroom soft rot.
- This lipopeptide exhibits potent antifungal activity against human-pathogenic fungi.
Purpose of the Study:
- To elucidate the mechanism of action of jagaricin.
- To assess the potential of jagaricin for agricultural and therapeutic applications.
Main Methods:
- Investigated jagaricin's effect on membrane integrity and ion flux (including Ca2+).
- Analyzed the role of the calcineurin pathway in fungal tolerance.
- Performed transcriptional profiling of pathogenic yeasts exposed to jagaricin.
Main Results:
- Jagaricin impairs membrane integrity, causing rapid ion influx into target cells.
- The calcineurin pathway is essential for tolerance in *Candida albicans*.
- Jagaricin induces cell wall strengthening, disrupts membrane potential-driven transport, and upregulates lipid transporters.
- Jagaricin exhibits low plant toxicity but has hemolytic effects.
Conclusions:
- Jagaricin's membrane-disrupting action is a promising antifungal mechanism.
- Potential applications exist in agriculture due to its efficacy against phytopathogenic fungi and low plant toxicity.
- Modifications are necessary for safe human therapeutic use due to observed hemolytic activity.
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