Homologs of the Acinetobacter baumannii AceI transporter represent a new family of bacterial multidrug efflux systems.
Homologs of the Acinetobacter baumannii AceI transporter represent a new family of bacterial multidrug efflux systems.
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DOI：
10.1128/mbio.01982-14
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发表时间：
2015-02-10
期刊：
影响因子：
6.4
通讯作者：
Paulsen IT
中科院分区：
文献类型：
--
作者：
Hassan KA;Liu Q;Henderson PJ;Paulsen IT
多药外排系统是细菌（包括对人类、动物和植物致病的细菌）对抗菌剂耐药性的主要原因。这些蛋白质在这些病原体中普遍存在，迄今已鉴定出五个细菌多药外排系统家族。通过使用转录组学和生物化学分析，我们最近确定了新的AceI（不动杆菌洗必泰外排）蛋白鲍曼不动杆菌，赋予抗药性的杀生物剂洗必泰，通过主动外排机制。与AceI同源的蛋白质在许多其他细菌物种的基因组中编码，并且在变形菌谱系中特别突出。在这项研究中，我们表达了23个同源的AceI和检查他们的阻力和/或运输概况。MIC分析表明，像AceI，许多同系物赋予耐洗必泰。许多AceI同系物赋予了对其他杀生物剂的抗性，包括苯扎氯铵、地喹氯铵、原黄素和吖啶黄素。我们进行了荧光运输试验，使用AceI同源物从副溶血性弧菌，并证实，耐药性都proflavine和acriflavine介导的主动外排机制。这些结果表明，这组AceI同系物代表了一个新的家庭的细菌多药外排泵，我们已经指定的蛋白细菌抗菌化合物外排（PACE）家庭的运输蛋白。细菌多药外排泵是一类重要的耐药决定因子，可以在迄今为止测序的每种细菌基因组中找到。这些转运蛋白对细菌细胞具有重要的保护功能，但在临床环境中是一个重要的问题，因为单一的外排系统可以介导对许多结构和机制不同的抗生素和杀生物剂的抗性。在这项研究中，我们表明，蛋白质相关的鲍曼不动杆菌AceI转运蛋白是一类新的多药外排系统，这是非常常见的变形菌：变形菌抗菌化合物外排（PACE）家庭。这是15年来描述的第一个新的多药外排泵系列。
Multidrug efflux systems are a major cause of resistance to antimicrobials in bacteria, including those pathogenic to humans, animals, and plants. These proteins are ubiquitous in these pathogens, and five families of bacterial multidrug efflux systems have been identified to date. By using transcriptomic and biochemical analyses, we recently identified the novel AceI (Acinetobacter chlorhexidine efflux) protein from Acinetobacter baumannii that conferred resistance to the biocide chlorhexidine, via an active efflux mechanism. Proteins homologous to AceI are encoded in the genomes of many other bacterial species and are particularly prominent within proteobacterial lineages. In this study, we expressed 23 homologs of AceI and examined their resistance and/or transport profiles. MIC analyses demonstrated that, like AceI, many of the homologs conferred resistance to chlorhexidine. Many of the AceI homologs conferred resistance to additional biocides, including benzalkonium, dequalinium, proflavine, and acriflavine. We conducted fluorimetric transport assays using the AceI homolog from Vibrio parahaemolyticus and confirmed that resistance to both proflavine and acriflavine was mediated by an active efflux mechanism. These results show that this group of AceI homologs represent a new family of bacterial multidrug efflux pumps, which we have designated the proteobacterial antimicrobial compound efflux (PACE) family of transport proteins. Bacterial multidrug efflux pumps are an important class of resistance determinants that can be found in every bacterial genome sequenced to date. These transport proteins have important protective functions for the bacterial cell but are a significant problem in the clinical setting, since a single efflux system can mediate resistance to many structurally and mechanistically diverse antibiotics and biocides. In this study, we demonstrate that proteins related to the Acinetobacter baumannii AceI transporter are a new class of multidrug efflux systems which are very common in Proteobacteria: the proteobacterial antimicrobial compound efflux (PACE) family. This is the first new family of multidrug efflux pumps to be described in 15 years.