Interaction of antibacterial compounds with RND efflux pumps in Pseudomonas aeruginosa.
Interaction of antibacterial compounds with RND efflux pumps in Pseudomonas aeruginosa.
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DOI：
10.3389/fmicb.2015.00660
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发表时间：
2015
影响因子：
5.2
通讯作者：
Ruggerone P
中科院分区：
文献类型：
--
作者：
Dreier J;Ruggerone P
铜绿假单胞菌感染由于固有的抗生素耐药性和这种病原体积累不同耐药机制的倾向而变得越来越难以治疗。耐药-结瘤-细胞分裂（RND）型多药e-lux泵的e-lux泵（例如，mexAB-oprM、mexCD-oprJ、mexEF-oprN和mexXY（-oprA）染色体编码的MexAB-OprM（MexAB-OprM）经常在临床分离株中检测到，并导致令人担忧的多药耐药表型。并非所有的抗生素都受到上述RND e Escherux泵的相同程度的影响。抗生素对抗生素活性的影响不仅在不同类别的抗生素之间存在差异，而且在同一抗生素家族的成员之间也存在差异。化合物-泵和化合物-溶剂相互作用的物理化学特征的细微差异在很大程度上决定了化合物如何受到电子束活性的影响。不同高分辨率技术的结合有助于深入了解这些分子机器的功能。本文综述了基于实验证据和计算机模拟的底物识别模式，重点是铜绿假单胞菌主要RND转运蛋白的泵亚基MexB。
Pseudomonas aeruginosa infections are becoming increasingly difficult to treat due to intrinsic antibiotic resistance and the propensity of this pathogen to accumulate diverse resistance mechanisms. Hyperexpression of efflux pumps of the Resistance-Nodulation-Cell Division (RND)-type multidrug efflux pumps (e.g., MexAB-OprM), chromosomally encoded by mexAB-oprM, mexCD-oprJ, mexEF-oprN, and mexXY (-oprA) is often detected in clinical isolates and contributes to worrying multi-drug resistance phenotypes. Not all antibiotics are affected to the same extent by the aforementioned RND efflux pumps. The impact of efflux on antibiotic activity varies not only between different classes of antibiotics but also between members of the same family of antibiotics. Subtle differences in physicochemical features of compound-pump and compound-solvent interactions largely determine how compounds are affected by efflux activity. The combination of different high-resolution techniques helps to gain insight into the functioning of these molecular machineries. This review discusses substrate recognition patterns based on experimental evidence and computer simulations with a focus on MexB, the pump subunit of the main RND transporter in P. aeruginosa.
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作者：
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