Spilanthol from Acmella oleracea (L.) R. K. Jansen induces metabolic alterations and impair an important virulence factor in Cryptococcus neoformans.

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.