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Multidrug efflux pumps as main players in intrinsic and acquired resistance to antimicrobials
Drug Resistance Updates ( IF 15.8 ) Pub Date : 2016-06-30 , DOI: 10.1016/j.drup.2016.06.007
Sara Hernando-Amado , Paula Blanco , Manuel Alcalde-Rico , Fernando Corona , Jose A. Reales-Calderón , María B. Sánchez , José L. Martínez

Multidrug efflux pumps constitute a group of transporters that are ubiquitously found in any organism. In addition to other functions with relevance for the cell physiology, efflux pumps contribute to the resistance to compounds used for treating different diseases, including resistance to anticancer drugs, antibiotics or antifungal compounds. In the case of antimicrobials, efflux pumps are major players in both intrinsic and acquired resistance to drugs currently in use for the treatment of infectious diseases. One important aspect not fully explored of efflux pumps consists on the identification of effectors able to induce their expression. Indeed, whereas the analysis of clinical isolates have shown that mutants overexpressing these resistance elements are frequently found, less is known on the conditions that may trigger expression of efflux pumps, hence leading to transient induction of resistance in vivo, a situation that is barely detectable using classical susceptibility tests. In the current article we review the structure and mechanisms of regulation of the expression of bacterial and fungal efflux pumps, with a particular focus in those for which a role in clinically relevant resistance has been reported.



中文翻译:

多药外排泵是内在和获得性抗微生物药耐药性的主要参与者

多药外排泵构成了在任何生物体中普遍存在的一组转运蛋白。除了与细胞生理相关的其他功能外,外排泵还有助于抵抗用于治疗不同疾病的化合物,包括对抗癌药,抗生素或抗真菌化合物的抵抗力。就抗菌剂而言,外排泵在对目前用于治疗传染病的药物的内在和获得性耐药性方面均起主要作用。尚未充分探索外排泵的一个重要方面在于鉴定能够诱导其表达的效应子。确实,尽管对临床分离株的分析表明,经常发现过表达这些抗性元件的突变体,在体内,使用经典药敏试验几乎无法检测到这种情况。在当前的文章中,我们综述了细菌和真菌外排泵表达的结构和调节机制,特别是那些已经报道了其在临床上具有抗药性的作用的泵。

更新日期:2016-06-30
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