Phylogenetic and functional characterisation of the Haemophilus influenzae multidrug efflux pump AcrB
Phylogenetic and functional characterisation of the Haemophilus influenzae multidrug efflux pump AcrB
复制标题
流感嗜血杆菌多药外排泵 AcrB 的系统发育和功能表征
DOI：
10.1038/s42003-019-0564-6
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发表时间：
2019
影响因子：
5.9
通讯作者：
Nishino Kunihiko
中科院分区：
文献类型：
--
作者：
Zwama Martijn;Yamaguchi Akihito;Nishino Kunihiko
革兰氏阴性菌的多药耐药可以通过多药外排泵的过度表达而产生，其可以挤出广泛的抗生素。在这里，我们描述了祖先流感嗜血杆菌外排泵AcrB（AcrB-Hi）。我们对数百种RND型转运蛋白进行了系统发育分析。我们发现AcrB-Hi是一种相对古老的外排泵，尽管如此，它仍然可以输出与大肠杆菌进化而来的同事相同范围的抗生素。AcrB-Hi不被外排泵抑制剂ABI-PP抑制，并能微弱地输出胆汁盐。这表明RND转运蛋白具有环境适应性。我们还解释了H.外膜孔蛋白OmpP 2介导流感病毒细胞对β-内酰胺类抗生素和新生霉素的敏感性。这种孔蛋白通过将药物泄漏回细胞来平衡AcrB-Hi流出。我们假设RND型泵的多药识别不是一种进化获得的能力，并且自古代混杂转运蛋白以来一直存在。
Multidrug resistance in Gram-negative bacteria can arise by the over-expression of multidrug efflux pumps, which can extrude a wide range of antibiotics. Here we describe the ancestralHaemophilus influenzaeefflux pump AcrB (AcrB-Hi). We performed a phylogenetic analysis of hundreds of RND-type transporters. We found that AcrB-Hi is a relatively ancient efflux pump, which nonetheless can export the same range of antibiotics as its evolved colleague fromEscherichia coli. AcrB-Hi was not inhibited by the efflux pump inhibitor ABI-PP, and could export bile salts weakly. This points to an environmental adaptation of RND transporters. We also explain the sensitivity ofH. influenzaecells to β-lactams and novobiocin by the outer membrane porin OmpP2. This porin counterbalances the AcrB-Hi efflux by leaking the drugs back into the cells. We hypothesise that multidrug recognition by RND-type pumps is not an evolutionarily acquired ability, and has been present since ancient promiscuous transporters.