Physically disrupting microorganism membranes to enable antibiotics to overcome resistance mechanisms that inhibit or excrete antibiotics has great potential for reducing antibiotic doses and rendering resistance mechanisms inert. We demonstrate the synergistic inactivation of a Gram-positive (Staphylococcus aureus) and two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria by combining 222 30 kV/cm electric pulses (EPs) or 500 20 kV/cm EPs with 300-ns EP duration with various antibiotics with different mechanisms of action is demonstrated. Doses of antibiotics that produced no inactivation in 10 min of exposure in solution with bacteria induced several log reductions under the influence of nanosecond EPs. Combining 2 μg/L or 20 μg/mL of rifampicin with the 30 kV/cm EPs enhanced Staphylococcus aureus inactivation compared with EPs alone, while only a few of the other combinations demonstrated improvement. Combining 2 μg/L or 20 μg/mL of mupirocin or rifampicin with either EP train enhanced E. coli inactivation compared with EPs alone. Combining 2 μg/L or 20 μg/mL of erythromycin or vancomycin with the 30 kV/cm EPs enhanced E. coli inactivation compared with EPs alone. These results indicate that EPs can make Gram-positive antibiotics efficient for inactivating Gram-negative bacteria with future studies required to optimize EP parameters for other antibiotics and Gram-negative bacteria.

中文翻译：

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纳秒电脉冲使用革兰氏阳性抗生素迅速增强了革兰氏阴性细菌的灭活作用。

物理破坏微生物膜以使抗生素能够克服抑制或排泄抗生素的耐药机制，具有减少抗生素剂量并使耐药机制呈惰性的巨大潜力。我们通过结合222个30 k​​V / cm电脉冲（EP）或500个20 kV / cm EP与300 ns结合来证明革兰氏阳性（金黄色葡萄球菌）和两个革兰氏阴性（大肠杆菌和铜绿假单胞菌）细菌的协同失活证明了使用各种具有不同作用机理的抗生素的EP持续时间。在纳秒级EP的影响下，在细菌溶液中暴露10分钟后未产生灭活作用的抗生素剂量引起数个对数减少。与单独的EP相比，将2μg/ L或20μg/ mL的利福平与30 kV / cm的EP结合可以增强金黄色葡萄球菌的失活，而其他组合中只有少数表现出改善。与单独的EP相比，将2μg/ L或20μg/ mL的mupirocin或rifampicin与任一EP训练组合均可增强大肠杆菌的灭活作用。与单独的EP相比，将2μg/ L或20μg/ mL的红霉素或万古霉素与30 kV / cm EP结合使用可增强大肠杆菌的灭活作用。这些结果表明，EPs可以使革兰氏阳性抗生素有效地灭活革兰氏阴性细菌，需要进一步研究来优化其他抗生素和革兰氏阴性细菌的EP参数。与单独的EP相比，大肠杆菌失活。与单独的EP相比，将2μg/ L或20μg/ mL的红霉素或万古霉素与30 kV / cm EP结合使用可增强大肠杆菌的灭活作用。这些结果表明，EPs可以使革兰氏阳性抗生素有效地灭活革兰氏阴性细菌，需要进一步研究来优化其他抗生素和革兰氏阴性细菌的EP参数。与单独的EP相比，大肠杆菌失活。与单独的EP相比，将2μg/ L或20μg/ mL的红霉素或万古霉素与30 kV / cm EP结合使用可增强大肠杆菌的灭活作用。这些结果表明，EPs可以使革兰氏阳性抗生素有效地灭活革兰氏阴性细菌，需要进一步研究来优化其他抗生素和革兰氏阴性细菌的EP参数。