Masi Muriel, Pagès Jean-Marie
CNRS-UMR 8619, Institut de Biophysique et de Biochimie Moléculaire et Cellulaire (IBBMC), Université Paris Sud, Orsay, France.
Open Microbiol J. 2013;7:22-33. doi: 10.2174/1874285801307010022. Epub 2013 Mar 22.
Antibiotic translocation across membranes of Gram-negative bacteria is a key step for the activity on their specific intracellular targets. Resistant bacteria control their membrane permeability as a first line of defense to protect themselves against external toxic compounds such as antibiotics and biocides. On one hand, resistance to small hydrophilic antibiotics such as ß-lactams and fluoroquinolones frequently results from the « closing » of their way in: the general outer membrane porins. On the other hand, an effective way out for a wide range of antibiotics is provided by TolC-like proteins, which are outer membrane components of multidrug efflux pumps. Accordingly, altered membrane permeability, including porin modifications and/or efflux pumps' overexpression, is always associated to multidrug resistance (MDR) in a number of clinical isolates. Several recent studies have highlighted our current understanding of porins/TolC structures and functions in Enterobacteriaceae. Here, we review the transport of antibiotics through the OmpF/C general porins and the TolC-like channels with regards to recent data on their structure, function, assembly, regulation and contribution to bacterial resistance. Because MDR strains have evolved global strategies to identify and fight our antibiotic arsenal, it is important to constantly update our global knowledge on antibiotic transport.
抗生素跨革兰氏阴性菌细胞膜的转运是其作用于特定细胞内靶点的关键步骤。耐药菌将控制其膜通透性作为第一道防线，以保护自身免受抗生素和杀菌剂等外部有毒化合物的侵害。一方面，对β-内酰胺类和氟喹诺酮类等亲水性小抗生素的耐药性通常源于其进入途径——通用外膜孔蛋白的“关闭”。另一方面，TolC样蛋白为多种抗生素提供了一条有效的排出途径，这类蛋白是多药外排泵的外膜成分。因此，在许多临床分离株中，包括孔蛋白修饰和/或外排泵过表达在内的膜通透性改变总是与多药耐药性（MDR）相关。最近的几项研究突出了我们目前对肠杆菌科细菌中孔蛋白/TolC结构和功能的理解。在此，我们结合有关其结构、功能、组装、调控以及对细菌耐药性贡献的最新数据，综述抗生素通过OmpF/C通用孔蛋白和TolC样通道的转运情况。由于多药耐药菌株已经进化出识别并对抗我们抗生素库的整体策略，持续更新我们关于抗生素转运的整体知识很重要。
