An effective response that combines prevention and treatment is still the most anticipated solution to the increasing incidence of antimicrobial resistance (AMR). As the phenomenon continues to evolve, AMR is driving an escalation of hard-to-treat infections and mortality rates. Over the years, bacteria have devised a variety of survival tactics to outwit the antibiotic's effects, yet given their great adaptability, unexpected mechanisms are still to be discovered. Over-expression of efflux pumps (EPs) constitutes the leading strategy of bacterial resistance, and it is also a primary driver in the establishment of multidrug resistance (MDR). Extensive efforts are being made to develop antibiotic resistance breakers (ARBs) with the ultimate goal of re-sensitizing bacteria to medications to which they have become unresponsive. EP inhibitors (EPIs) appear to be the principal group of ARBs used to impair the efflux system machinery. Due to the high toxicity of synthetic EPIs, there is a growing interest in natural, safe, and innocuous ones, whereby plant extracts emerge to be excellent candidates. Besides EPIs, further alternatives are being explored including the development of nanoparticle carriers, biologics, and phage therapy, among others. What roles do EPs play in the occurrence of MDR? What weapons do we have to thwart EP-mediated resistance? What are the obstacles to their development? These are some of the core questions addressed in the present review.

中文翻译：

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阻止细菌外排泵介导的抵抗的方法是什么？

预防和治疗相结合的有效应对措施仍然是应对日益增加的抗菌素耐药性 (AMR) 发生率的最令人期待的解决方案。随着这一现象的不断发展，AMR 正在推动难以治疗的感染和死亡率的上升。多年来，细菌已经设计出多种生存策略来战胜抗生素的作用，但鉴于它们具有很强的适应性，仍有待发现意想不到的机制。外排泵（EPs）的过度表达构成了细菌耐药性的主要策略，也是建立多药耐药性（MDR）的主要驱动因素。正在大力开发抗生素抗药性破坏剂 (ARB)，其最终目标是使细菌对它们已经变得无反应的药物重新敏感。EP 抑制剂 (EPI) 似乎是用于损害外排系统机制的 ARB 的主要组。由于合成 EPI 的高毒性，人们对天然、安全和无害的 EPI 越来越感兴趣，因此植物提取物成为极好的候选者。除了 EPI，正在探索其他替代方案，包括开发纳米颗粒载体、生物制剂和噬菌体疗法等。EP 在 MDR 的发生中起什么作用？我们有什么武器来阻止 EP 介导的抵抗？他们发展的障碍是什么？这些是本次审查中解决的一些核心问题。因此，植物提取物成为优秀的候选者。除了 EPI，正在探索其他替代方案，包括开发纳米颗粒载体、生物制剂和噬菌体疗法等。EP 在 MDR 的发生中起什么作用？我们有什么武器来阻止 EP 介导的抵抗？他们发展的障碍是什么？这些是本次审查中解决的一些核心问题。因此，植物提取物成为优秀的候选者。除了 EPI，正在探索其他替代方案，包括开发纳米颗粒载体、生物制剂和噬菌体疗法等。EP 在 MDR 的发生中起什么作用？我们有什么武器来阻止 EP 介导的抵抗？他们发展的障碍是什么？这些是本次审查中解决的一些核心问题。