Schuldiner Shimon
Department of Biological Chemistry, Institute of Life Sciences, Silberman Bldg. 1-339, Edmond J. Safra Campus, Hebrew University of Jerusalem, Givat Ram, Jerusalem, 91904, Israel.
Res Microbiol. 2018 Sep-Oct;169(7-8):357-362. doi: 10.1016/j.resmic.2018.02.006. Epub 2018 Mar 21.
Multidrug transporters function in a coordinated mode to provide an essential first-line defense mechanism that prevents antibiotics from reaching lethal concentrations, until a number of stable efficient adaptations occur that allow survival. Single-component efflux transporters remove the toxic compounds from the cytoplasm to the periplasmic space where TolC-dependent transporters expel them from the cell. The close interaction between the two types of transporters ensures handling of a wide range of xenobiotics and prevents rapid leak of the hydrophobic substrates back into the cell. In this review, we discuss the concept of the bacterial effluxome of the Gram-negative Escherichia coli that is the entire set of transporters expressed at a given time, under defined conditions. The process of identification of its members and the elucidation of the nature of the interactions throw a novel light on the roles of transporters in bacterial physiology and drug resistance development. We anticipate that the concept of an effluxome where each member contributes to the removal of noxious chemicals from the cell should contribute to improving the present strategy of searching for transport inhibitors as adjuvants of existing antibiotics and provide novel targets for this urgent undertaking.
多药转运蛋白以协同模式发挥作用，提供一种重要的一线防御机制，防止抗生素达到致死浓度，直到出现一些稳定的有效适应性变化以实现存活。单组分外排转运蛋白将有毒化合物从细胞质转运到周质空间，在那里依赖TolC的转运蛋白将它们排出细胞。这两种转运蛋白之间的紧密相互作用确保了对多种异生素的处理，并防止疏水性底物迅速泄漏回细胞。在本综述中，我们讨论了革兰氏阴性大肠杆菌细菌外排体的概念，即给定时间内在特定条件下表达的所有转运蛋白。鉴定其成员的过程以及阐明相互作用的性质，为转运蛋白在细菌生理学和耐药性发展中的作用提供了新的视角。我们预计，外排体的概念，即每个成员都有助于从细胞中清除有害化学物质，应该有助于改进目前寻找转运抑制剂作为现有抗生素佐剂的策略，并为这一紧迫任务提供新的靶点。
