Dictyostelium discoideum-assisted pharmacognosy of plant resources for discovering antivirulence molecules targetingKlebsiella pneumoniae

Abstract

ABSTRACTThe rise of antibiotic-resistant bacterial strains poses a significant global health challenge, underscoring the critical need for innovative strategies to address this threat. Natural products and their derivatives have emerged as a promising reservoir for drug discovery. The social amoebaDictyostelium discoideumis an advantageous model organism in this effort. Using this invertebrate model, we introduce a novel perspective to screen natural plant extracts for molecules with potential antivirulence activity. As a proof of concept, we established a simple high-throughput assay to screen for antivirulence molecules targetingKlebsiella pneumoniaeamong extracts ofHelenium aromaticum. Thus, we aimed to identify compounds attenuatingK. pneumoniaevirulence without inducing cytotoxic effects on amoeba cells. Notably, the methanolic root extract ofH. aromaticumbut not other extracts fulfilled these prerequisites. Further analysis via UHPLC-ESI-MS/MS led to the identification of 24 chemical compounds boasting potential antivirulence attributes. This research underscores the potential of employingD. discoideum-assisted pharmacognosy for unearthing novel antivirulence agents against multidrug-resistant pathogens.Table of Content Graphic