Guanethidine Enhances the Antibacterial Activity of Rifampicin Against Multidrug-Resistant Bacteria

文献类型： 外文期刊

第一作者： Zhao, Xiaoou

作者： Zhao, Xiaoou;Zhang, Zhendu;Liu, Lizai;Wang, Duojia;Zhang, Xin;Zhao, Luobing;Zhao, Yunhui;Jin, Xiangshu;Wang, Lei;Liu, Xiaoxiao

作者机构：

关键词： antibiotic adjuvant; guanethidine; rifampicin; proton motive force; antibiotic resistance

期刊名称：MICROORGANISMS （ 影响因子：4.2； 五年影响因子：4.6 ）

ISSN：

年卷期： 2024 年 12 卷 11 期

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收录情况： SCI

摘要： The escalating global threat of antibiotic resistance necessitates innovative strategies, such as the combination of antibiotics with adjuvants. Monotherapy with rifampicin is more likely to induce resistance in pathogens compared to other antibiotics. Herein, we found that the antihypertensive drug guanethidine enhanced the activity of rifampicin against certain clinically resistant Gram-negative bacteria, resulting in a reduction of up to 128-fold in the minimum inhibitory concentration. In infected animal models, this combination has achieved treatment benefits, including increased survival and decreased bacterial burden. The antimicrobial mechanism of guanethidine in synergy with rifampicin involves the disruption of the outer membrane of Gram-negative bacteria, leading to dissipation of the proton motive force. This results in an increase in reactive oxygen species and a reduction in ATP synthesis, severely disturbing energy metabolism and ultimately increasing bacterial mortality. In summary, guanethidine has the potential to become a novel adjuvant for rifampicin, offering a new option for the treatment of clinical Gram-negative bacterial infections.

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