细菌外排转运蛋白的多特异性——是福还是祸？
Bacterial efflux transporters' polyspecificity - a gift and a curse?
机构信息
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73072, United States.
Department of Physics, University of Cagliari, 09042 Monserrato (Cagliari), Italy.
出版信息
Curr Opin Microbiol. 2021 Jun;61:115-123. doi: 10.1016/j.mib.2021.03.009. Epub 2021 Apr 30.
Abstract
All mechanisms of clinical antibiotic resistance benefit from activities of polyspecific efflux pumps acting to reduce intracellular accumulation of toxins and antibiotics. In Gram-negative bacteria, the major polyspecific efflux transporters belong to the Resistance-Nodulation-cell Division (RND) superfamily of proteins, which are capable of expelling thousands of structurally diverse compounds. Recent structural and functional advances generated novel insights into mechanisms underlying the biochemical versatility of RND transporters. This opinion article reviews these mechanisms and discusses implications of the polyspecificity of RND transporters for bacterial survival and for the development of efflux pump inhibitors effective in clinics.
摘要
所有临床抗生素耐药机制都得益于多特异性外排泵的活动，这些泵可减少细胞内毒素和抗生素的积累。在革兰氏阴性菌中，主要的多特异性外排转运蛋白属于抗性-结节-分裂（RND）蛋白超家族，它们能够排出数千种结构不同的化合物。最近的结构和功能进展为 RND 转运蛋白生化多功能性的机制提供了新的见解。本文综述了这些机制，并讨论了 RND 转运蛋白的多特异性对细菌生存和开发临床上有效的外排泵抑制剂的意义。
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