期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1982
卷号：79
期号：21
页码：6693-6697
DOI：10.1073/pnas.79.21.6693
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：At pH 5.0, the electrical potential (delta psi, interior negative) across the plasma membrane of Staphylococcus aureus exhibits a minimum of -85 to -90 mV; the pH gradient (delta pH, interior alkaline) across the membrane approximates a maximum of about -100 mV. Under these conditions, uptake of the aminoglycoside gentamicin is negligible, and viability of the organism is not impaired by the antibiotic. In contrast, at pH 7.5, at which delta psi is about -130 mV and delta pH is 0, gentamicin uptake is observed and the drug markedly decreases viability. Dramatically, when the ionophore nigericin is added at pH 5.0, gentamicin uptake is induced, there is a striking decrease in viability, and the effect is associated with an increase in delta psi at the expense of delta pH. Consistently, valinomycin, which dissipates delta psi in the presence of potassium, abolishes gentamicin uptake and killing. In addition, from pH 5.0 to pH 7.5, there is a direct relationship between the magnitude of delta psi and both gentamicin uptake and its bactericidal effect. However, a threshold delta psi of -75 to -90 mV is apparently necessary to initiate uptake and killing. These observations provide a strong indication that delta psi plays a critical role in the uptake and antibacterial action of gentamicin and suggest that nigericin-like ionophores may be clinically useful in synergy with aminoglycosides.
