Seukep Armel Jackson, Mbuntcha Helene Gueaba, Kuete Victor, Chu Yindi, Fan Enguo, Guo Ming-Quan
CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture, Wuhan Botanical Garden, Chinese Academy of Sciences, Wuhan 437004, China.
Department of Biomedical Sciences, Faculty of Health Sciences, University of Buea, Buea P.O. Box 63, Cameroon.
Antibiotics (Basel). 2022 Sep 21;11(10):1287. doi: 10.3390/antibiotics11101287.
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.
一种将预防与治疗相结合的有效应对措施，仍然是应对日益增加的抗菌药物耐药性（AMR）发生率最值得期待的解决方案。随着这一现象不断演变，AMR正在推动难治性感染和死亡率的上升。多年来，细菌设计了各种生存策略来对抗抗生素的作用，但鉴于它们强大的适应性，仍有一些意想不到的机制有待发现。外排泵（EPs）的过度表达是细菌耐药的主要策略，也是多重耐药（MDR）形成的主要驱动因素。人们正在广泛努力开发抗生素耐药性突破剂（ARBs），其最终目标是使对已无反应的药物重新敏感的细菌恢复敏感性。EP抑制剂（EPIs）似乎是用于破坏外排系统机制的主要ARBs类别。由于合成EPIs的高毒性，人们对天然、安全且无害的EPIs的兴趣与日俱增，植物提取物成为了极佳的候选者。除了EPIs，人们还在探索其他替代方案，包括开发纳米颗粒载体、生物制品和噬菌体疗法等。EPs在MDR的发生中起什么作用？我们有哪些武器来对抗EP介导的耐药性？它们的发展面临哪些障碍？这些是本综述中探讨的一些核心问题。
