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

Area of Science:

• Microbiology
• Pharmacology
• Natural Products Chemistry

Background:

• Rising threat of multidrug-resistant Acinetobacter baumannii (MDR AB) infections.
• Need for novel therapeutic strategies against MDR AB.
• Traditional use of Senecio scandens as a medicinal herb.

Purpose of the Study:

• Investigate the in vitro antibacterial activity of Senecio scandens crude extract against MDR AB.
• Elucidate the mechanism of action of the extract and its active compounds.
• Identify potential new therapeutic agents for MDR AB infections.

Main Methods:

• Antibiotic sensitivity testing and microbroth dilution (MIC/MBC) on clinical MDR AB strains.
• Time-kill curve analysis for bactericidal kinetics.
• Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) for structural analysis.
• Proteomics, molecular docking, and quantitative Polymerase Chain Reaction (qPCR) to identify and validate molecular targets.

Main Results:

• Senecio scandens extract exhibited concentration-dependent bactericidal effects against MDR AB (MIC = 640 μg/mL).
• The extract disrupted bacterial cell wall and membrane integrity.
• Proteomic analysis identified downregulation of membrane-related proteins msbA and lptD.
• Linarin and hyperoside were identified as key active compounds, downregulating msbA and lptD mRNA and protein expression, and showed strong binding to these targets via molecular docking.
• Linarin and hyperoside demonstrated antibacterial activity with MIC = 312.5 μmol/L.

Conclusions:

• Senecio scandens extract possesses significant in vitro antibacterial activity against MDR AB.
• Linarin and hyperoside are novel inhibitors of MDR AB, acting by downregulating msbA and lptD, which compromises outer membrane integrity.
• These findings highlight the potential of Senecio scandens derived compounds as new therapeutic candidates against MDR AB infections.