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首页> 外文期刊>Journal of Molecular Biology >Breaching the Barrier: Quantifying Antibiotic Permeability across Gram-negative Bacterial Membranes
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Breaching the Barrier: Quantifying Antibiotic Permeability across Gram-negative Bacterial Membranes

机译：违反屏障：量化革兰阴性细菌膜的抗生素渗透性

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The double-membrane cell envelope of Gram-negative bacteria is a sophisticated barrier that facilitates the uptake of nutrients and protects the organism from toxic compounds. An antibiotic molecule must find its way through the negatively charged lipopolysaccharide layer on the outer surface, pass through either a porin or the hydrophobic layer of the outer membrane, then traverse the hydrophilic peptidoglycan layer only to find another hydrophobic lipid bilayer before it finally enters the cytoplasm, where it typically finds its target. This complex uptake pathway with very different physico-chemical properties is one reason that Gram-negative are intrinsically protected against multiple classes of antibiotic-like molecules, and is likely the main reason that in vitro target-based screening programs have failed to deliver novel antibiotics for these organisms. Due to the lack of general methods available for quantifying the flux of drugs into the cell, little is known about permeation rates, transport pathways and accumulation at the target sites for particular molecules. Here we summarize the current tools available for measuring antibiotic uptake across the different compartments of Gramnegative bacteria. (C) 2019 Elsevier Ltd. All rights reserved.
机译：革兰氏阴性细菌的双膜细胞包络是一种复杂的屏障，促进了营养素的摄取并保护生物免受毒性化合物。抗生素分子必须通过外表面上的带负电荷的脂多糖层发现，通过孔隙或外膜的疏水层，然后遍历亲水性肽聚糖层，仅在其最终进入之前找到另一种疏水性脂质双层。细胞质，通常发现其目标。具有非常不同的物理化学性质的这种复杂的摄取途径是革兰氏阴性的一种原因是针对多种抗生素样分子固有保护，并且可能是在体外基于目标的筛查计划未能提供新型抗生素的主要原因对于这些生物。由于缺乏可用于量化药物的通量进入细胞的一般方法，对特定分子的靶位点的渗透速率，运输途径和积累很少几乎是已知的。在这里，我们总结了目前可用于测量在革兰氏细菌的不同隔室中的抗生素摄取的工具。 （c）2019 Elsevier Ltd.保留所有权利。

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