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Membrane potential and gentamicin uptake in Staphylococcus aureus

S M Mates, E S Eisenberg, L J Mandel

    Proceedings of the National Academy of Sciences of the United States of America
    |November 1, 1982
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    Electrical potential (delta psi) across bacterial membranes is critical for gentamicin uptake and killing. A threshold delta psi is needed for aminoglycoside antibiotic action, suggesting synergistic therapies.

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    Area of Science:

    • Microbiology
    • Molecular Biology
    • Biophysics

    Background:

    • Gentamicin, an aminoglycoside antibiotic, is crucial for treating Gram-negative bacterial infections.
    • Bacterial membrane potential, including electrical potential (delta psi) and pH gradient (delta pH), influences drug transport and efficacy.
    • Staphylococcus aureus is a significant human pathogen, and understanding its susceptibility to antibiotics is vital.

    Purpose of the Study:

    • To investigate the role of electrical potential (delta psi) and pH gradient (delta pH) in the uptake and bactericidal activity of gentamicin in Staphylococcus aureus.
    • To determine the relationship between membrane potential and gentamicin's efficacy.
    • To explore potential synergistic therapeutic strategies involving ionophores and aminoglycosides.

    Main Methods:

    • Utilized Staphylococcus aureus cultures at varying pH levels (5.0 and 7.5) to manipulate delta psi and delta pH.
    • Employed ionophores nigericin and valinomycin to specifically alter membrane potential and pH gradient.
    • Quantified gentamicin uptake and assessed bacterial viability through viability assays.
    • Correlated changes in delta psi and delta pH with gentamicin's antibacterial effects.

    Main Results:

    • At pH 5.0, low delta psi and high delta pH correlated with negligible gentamicin uptake and no loss of viability.
    • At pH 7.5, higher delta psi and dissipated delta pH resulted in significant gentamicin uptake and decreased viability.
    • Nigericin induced gentamicin uptake and killing at pH 5.0 by increasing delta psi at the expense of delta pH.
    • Valinomycin abolished gentamicin uptake and killing, confirming delta psi's critical role.
    • A direct relationship was observed between delta psi magnitude and gentamicin's bactericidal effect, with a threshold of -75 to -90 mV required.

    Conclusions:

    • Electrical potential (delta psi) plays a critical role in the uptake and antibacterial action of gentamicin against Staphylococcus aureus.
    • A minimum threshold of delta psi is necessary for gentamicin to initiate uptake and exert its bactericidal effect.
    • Ionophores like nigericin, which modulate delta psi, may hold potential for synergistic use with aminoglycosides in clinical settings.