Linarin and Hyperoside Inhibit lptD/msbA to Disrupt Membranes of Multidrug-Resistant Acinetobacter baumannii

Against the backdrop of rising multidrug-resistant <i>Acinetobacter baumannii</i> (MDR AB) threats, this study explores the in vitro antibacterial activity and mechanism of <i>Senecio scandens</i> (a Miao ethnic medicinal herb) crude extract. Using 10 clinical MDR AB strains, we reassessed antibiotic sensitivity and then applied microbroth dilution to determine MIC/MBC, time-kill curves for bactericidal kinetics, and SEM/TEM for structural changes. Proteomics identified downregulated proteins, cross-referenced with VFDB/CARD to target membrane-related proteins (msbA, lptD), while molecular docking validated the strong binding of linarin/hyperoside to these targets. qPCR confirmed lptD/msbA mRNA downregulation (<i>p</i> < 0.05) by linarin/hyperoside (MIC = 312.5 μmol/L). The extract showed concentration-dependent bactericidal effects (MIC = 640 μg/mL), disrupting cell wall/membrane integrity. This study first reveals that linarin and hyperoside inhibit MDR AB by downregulating lptD/msbA, compromising outer membrane integrity, offering novel therapeutic candidates.