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

The 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 amoeba Dictyostelium discoideum is 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 targeting Klebsiella pneumoniae among extracts of Helenium aromaticum. Thus, we aimed to identify compounds attenuating K. pneumoniae virulence without inducing cytotoxic effects on amoeba cells. Notably, the methanolic root extract of H. aromaticum but 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 employing D. discoideum-assisted pharmacognosy for unearthing novel antivirulence agents against multidrug-resistant pathogens. Table of Content Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=87 SRC="FIGDIR/small/564015v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@17530faorg.highwire.dtl.DTLVardef@e28259org.highwire.dtl.DTLVardef@dbc87eorg.highwire.dtl.DTLVardef@147de2d_HPS_FORMAT_FIGEXP M_FIG C_FIG