PDF(Pubmed)
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.
摘要：
全球细菌感染呈上升趋势,对细菌的耐药性逐渐使现有的抗生素无效。因此,迫切需要发现新的策略。细胞代谢是调节细菌耐药性的关键因素,这离不开高能物质的利用，这表明高能物质可能与细菌耐药性有关。在这项研究中,我们发现单磷酸腺苷（AMP）可以增强庆大霉素对耐庆大霉素金黄色葡萄球菌的杀菌效果。这种协同作用可以推广用于不同的抗生素和革兰氏阳性或革兰氏阴性细菌。我们还验证了AMP逆转抗生素抗性的机制涉及通过三羧酸循环增强质子动力以增加抗生素摄取。同时,AMP增加氧化应激诱导的细胞死亡。本研究提出了采用低剂量抗生素控制耐药菌的策略,这对未来的药物开发和细菌控制很重要。
