Bacteria harness an impressive repertoire of resistance mechanisms to evade the inhibitory action of antibiotics. One such mechanism involves efflux pump-mediated extrusion of drugs from the bacterial cell, which significantly contributes to multidrug resistance. Intriguingly, most drug efflux pumps are chromosomally encoded components of the intrinsic antibiotic resistome. In addition, in terms of xenobiotic detoxification, bacterial efflux systems often exhibit significant levels of functional redundancy. Efflux pumps are also considered to be highly conserved; however, the extent of conservation in many bacterial species has not been reported and the majority of genes that encode efflux pumps appear to be dispensable for growth. These observations, in combination with an increasing body of experimental evidence, imply alternative roles in bacterial physiology. Indeed, the ability of efflux pumps to facilitate antibiotic resistance could be a fortuitous by-product of ancient physiological functions. Using Escherichia coli as a model organism, we here evaluated the evolutionary conservation of drug efflux pumps and we provide phylogenetic analysis of the major efflux families. We show the E. coli drug efflux system has remained relatively stable and the majority (∼80%) of pumps are encoded in the core genome. This analysis further supports the importance of drug efflux pumps in E. coli physiology. In this review, we also provide an update on the roles of drug efflux pumps in the detoxification of endogenously synthesized substrates and pH homeostasis. Overall, gaining insight into drug efflux pump conservation, common evolutionary ancestors, and physiological functions could enable strategies to combat these intrinsic and ancient elements.

中文翻译：

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大肠杆菌药物流出泵的进化保守支持生理功能。


细菌利用一系列令人印象深刻的耐药机制来逃避抗生素的抑制作用。其中一种机制涉及外排泵介导的药物从细菌细胞中的挤出，这对多药耐药性有显着贡献。有趣的是，大多数药物外排泵是内在抗生素抗性组的染色体编码成分。此外，在外源物解毒方面，细菌外排系统通常表现出显着的功能冗余。外排泵也被认为是高度保守的；然而，许多细菌物种的保守程度尚未被报道，并且大多数编码外排泵的基因似乎对于生长来说是可有可无的。这些观察结果与越来越多的实验证据相结合，暗示着细菌生理学中的替代作用。事实上，外排泵促进抗生素耐药性的能力可能是古代生理功能的偶然副产品。使用大肠杆菌作为模式生物，我们评估了药物外排泵的进化保守性，并提供了主要外排家族的系统发育分析。我们表明大肠杆菌药物流出系统保持相对稳定，并且大多数（~80％）泵在核心基因组中编码。该分析进一步支持药物外排泵在大肠杆菌生理学中的重要性。在这篇综述中，我们还提供了药物外排泵在内源合成底物解毒和 pH 稳态中作用的最新信息。 总体而言，深入了解药物外排泵保护、共同进化祖先和生理功能可以制定对抗这些内在和古老元素的策略。