Breaking the Permeability Barrier of Escherichia coli by Controlled Hyperporination of the Outer Membrane
Breaking the Permeability Barrier of Escherichia coli by Controlled Hyperporination of the Outer Membrane
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DOI：
10.1128/aac.01882-16
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发表时间：
2016-12-01
影响因子：
4.9
通讯作者：
Zgurskaya, Helen I.
中科院分区：
文献类型：
--
作者：
Krishnamoorthy, Ganesh;Wolloscheck, David;Zgurskaya, Helen I.
在革兰氏阴性菌中，抗生素通过外膜的缓慢被动吸收与主动外排转运体之间的协同关系产生了一个渗透性屏障，有效地降低了抗生素在细胞中的有效浓度，从而降低了它们的活性。为了分析主动外排和被动屏障对抗生素活性的相对贡献，我们构建了外膜通透性可控的大肠杆菌菌株。菌株表现出一个大孔，不区分化合物的亲水性，并使细胞对各种抗菌剂敏感。我们发现，抗生素在这些菌株中的效果受到主动外排或缓慢吸收或两者兼而有之的特殊影响，并反映了外膜屏障特性、外排泵功能和抗生素抑制活性的差异。我们的研究结果确定了通过外排抑制和外膜渗透来增强活性的最佳候选抗生素。
In Gram-negative bacteria, a synergistic relationship between slow passive uptake of antibiotics across the outer membrane and active efflux transporters creates a permeability barrier, which efficiently reduces the effective concentrations of antibiotics in cells and, hence, their activities. To analyze the relative contributions of active efflux and the passive barrier to the activities of antibiotics, we constructed Escherichia coli strains with controllable permeability of the outer membrane. The strains expressed a large pore that does not discriminate between compounds on the basis of their hydrophilicity and sensitizes cells to a variety of antibacterial agents. We found that the efficacies of antibiotics in these strains were specifically affected by either active efflux or slow uptake, or both, and reflect differences in the properties of the outer membrane barrier, the repertoire of efflux pumps, and the inhibitory activities of antibiotics. Our results identify antibiotics which are the best candidates for the potentiation of activities through efflux inhibition and permeabilization of the outer membrane.