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Published on: December 2, 2022
Spilanthol from Acmella oleracea (L.) R. K. Jansen induces metabolic alterations and impair an important virulence
Aline G Silva1, Renata P Costa2, Yohana P Calegari-Alves3
1Post-graduation Program in Pharmaceutical Sciences, Federal University of Rio Grande do Sul, Brazil; Laboratory of Molecular Microbiology and Proteomics, Federal University of Rio Grande do Sul, Brazil.
Introduction:
Cryptococcus neoformans is a critical opportunistic fungal pathogen, responsible for cryptococcosis with high mortality rates, particularly in HIV patients, largely due to escalating antifungal resistance and limited treatment options. The World Health Organization has critically categorized this yeast, highlighting the urgent need for novel therapeutic strategies. This study investigates spilanthol, a prominent N-alkylamide from Acmella oleracea (jambu), a Brazilian medicinal plant known for its diverse bioactivities.
Methods:
Through shotgun proteomics, we identified differences in the protein profiles of cells exposed to spilanthol, when comparing to control (not exposed). A bioinformatic approach was used to analyze the metabolic changes and molecular characteristics of the proteome.
Results:
Our data suggests general alterations in energy metabolism, oxidative stress, and a reduction in a significant cryptococcal virulence factor, urease, which was experimentally confirmed. Moreover, spilanthol induces modifications in the cell membrane, as confirmed by cell leakage and a decrease in ergosterol content.
Conclusion:
Spilanthol induced metabolic and morphological alterations, triggered profound oxidative stress, and suppressed the virulence factor urease, potentially elucidating the mechanism responsible for its antifungal properties.
Insights
Spilanthol, derived from the jambu plant, shows promise as an antifungal agent by disrupting fungal metabolism, increasing oxidative stress, and reducing the virulence factor urease in Cryptococcus neoformans.
Area of Science:
- Mycology
- Pharmacology
- Biochemistry
Background:
- Cryptococcus neoformans causes life-threatening cryptococcosis, especially in immunocompromised individuals.
- Rising antifungal resistance necessitates novel therapeutic strategies.
- Spilanthol, from Acmella oleracea, is explored for its bioactivity.
Purpose of the Study:
- To investigate the antifungal mechanisms of spilanthol against Cryptococcus neoformans.
- To identify molecular and metabolic changes induced by spilanthol.
Main Methods:
- Shotgun proteomics to analyze protein expression differences.
- Bioinformatic analysis of metabolic pathways and molecular characteristics.
- Experimental confirmation of urease activity and cell membrane integrity.
Main Results:
- Spilanthol alters energy metabolism and induces oxidative stress.
- Significant reduction in the virulence factor urease was observed and confirmed.
- Spilanthol modifies the fungal cell membrane, increasing leakage and decreasing ergosterol.
Conclusions:
- Spilanthol exhibits antifungal properties by inducing metabolic and morphological changes.
- Oxidative stress and suppression of urease are key mechanisms of spilanthol's action.
- Spilanthol represents a potential new therapeutic lead for cryptococcosis treatment.
