Adenosine Monophosphate as a Metabolic Adjuvant Enhances Antibiotic Efficacy against Drug-Resistant Bacterial Pathogens

Pharmaceuticals Pub Date : 2024-07-11 DOI:10.3390/ph17070933
Wenxuan Zhang, Zhenyi Wu, Zulifukeer Maituersong, Ting Wang, Yubin Su
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Abstract

Global bacterial infections are on the rise, and drug resistance to bacteria is gradually rendering existing antibiotics ineffective. Therefore, the discovery of new strategies is urgently needed. Cellular metabolism is a key factor in the regulation of bacterial drug resistance, which cannot be separated from the utilization of energetic substances, suggesting that energetic substances may be associated with bacterial drug resistance. In this study, we found that adenosine monophosphate (AMP) can enhance the bactericidal effect of gentamicin against gentamicin-resistant Staphylococcus aureus. This synergistic effect can be generalized for use with different antibiotics and Gram-positive or Gram-negative bacteria. We also validated that the mechanism of AMP reversal of antibiotic resistance involves enhancing the proton motive force via the tricarboxylic acid cycle to increase antibiotic uptake. Simultaneously, AMP increases oxidative stress-induced cell death. This study presents a strategy for adopting low-dose antibiotics to control drug-resistant bacteria, which is important for future drug development and bacterial control.
作为代谢佐剂的单磷酸腺苷可增强抗生素对耐药细菌病原体的疗效
全球细菌感染呈上升趋势,细菌的耐药性正逐渐使现有抗生素失效。因此,迫切需要发现新的策略。细胞代谢是调控细菌耐药性的关键因素,而细胞代谢离不开能量物质的利用,这表明能量物质可能与细菌耐药性有关。本研究发现,单磷酸腺苷(AMP)能增强庆大霉素对耐庆大霉素金黄色葡萄球菌的杀菌作用。这种协同作用可用于不同的抗生素和革兰氏阳性或阴性细菌。我们还验证了 AMP 逆转抗生素耐药性的机制涉及通过三羧酸循环增强质子动力,从而增加抗生素的吸收。同时,AMP 会增加氧化应激诱导的细胞死亡。这项研究提出了一种采用低剂量抗生素控制耐药细菌的策略,对未来的药物开发和细菌控制具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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