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Polycations as outer membrane-disorganizing agents.

M Vaara, T Vaara

    Antimicrobial Agents and Chemotherapy
    |July 1, 1983
    PubMed
    Summary
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    Polycationic agents like protamine and lysine20 disrupt bacterial outer membranes by releasing lipopolysaccharide. Polymyxin B nonapeptide, however, increases outer membrane permeability to hydrophobic molecules.

    Area of Science:

    • Microbiology
    • Bacterial Outer Membrane Structure
    • Polycationic Agent Interactions

    Background:

    • The bacterial outer membrane is a critical barrier, and understanding its disruption is key to developing new antimicrobial strategies.
    • Polycationic agents are known to interact with bacterial membranes, but their specific effects can vary.

    Purpose of the Study:

    • To investigate and differentiate the outer membrane-disorganizing effects of specific polycationic agents on Salmonella typhimurium.
    • To compare the actions of protamine, lysine20, and polymyxin B nonapeptide on bacterial membrane integrity and permeability.

    Main Methods:

    • Treatment of smooth Salmonella typhimurium with protamine, lysine20, and polymyxin B nonapeptide for 10 minutes.
    • Analysis of lipopolysaccharide release, bacterial sensitization to sodium dodecyl sulfate, and permeability to hydrophobic probes (fusidic acid, actinomycin D).

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  • Assessment of bactericidal activity, beta-lactamase leakage, and visualization of outer membrane changes using thin-section electron microscopy.

    • Main Results:

    • Protamine and lysine20 released 20-30% of lipopolysaccharide and sensitized bacteria to sodium dodecyl sulfate, but did not increase permeability to hydrophobic probes.
    • Polymyxin B nonapeptide did not release lipopolysaccharide or sensitize bacteria to sodium dodecyl sulfate, but increased outer membrane permeability to hydrophobic probes.
    • Electron microscopy revealed distinct morphological changes: wrinkled membranes for protamine/lysine20 and finger-like projections for polymyxin B nonapeptide.

    Conclusions:

    • Two distinct mechanisms of outer membrane disorganization by polycationic agents were identified.
    • Protamine and lysine20 primarily affect lipopolysaccharide integrity, while polymyxin B nonapeptide targets outer membrane permeability.
    • These findings highlight the diverse ways polycationic agents can compromise bacterial outer membrane function.