Receptor polymorphism restricts contact-dependent growth inhibition to members of the same species.
Receptor polymorphism restricts contact-dependent growth inhibition to members of the same species.
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DOI：
10.1128/mbio.00480-13
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发表时间：
2013-07-23
期刊：
影响因子：
6.4
通讯作者：
Hayes CS
中科院分区：
文献类型：
--
作者：
Ruhe ZC;Wallace AB;Low DA;Hayes CS
表达接触依赖性生长抑制（CDI）系统的细菌胜过缺乏免疫力的同胞，表明CDI介导细胞间竞争。为了进一步探索CDI在竞争中的作用，我们确定了来自大肠杆菌EC 93的CDIEC 93系统的靶细胞范围。CdiAEC 93效应蛋白识别广泛保守的BamA蛋白作为受体，但大肠杆菌EC 93不抑制其他肠细菌物种。BamA的预测膜拓扑结构表明，其三个细胞外环物种之间的差异很大，这表明环的异质性可能控制CDI特异性。与该假设一致，其他肠细菌在大肠杆菌bamA表达后对CDIEC 93敏感，并且当bamA被来自其他物种的等位基因替换时，大肠杆菌细胞变得对CDIEC 93具有抗性。我们的数据表明BamA环6和7形成CdiAEC 93结合表位，并且它们在物种之间的变化限制了CDIEC 93靶细胞选择。虽然BamA环6和7在物种之间差异很大，但这些区域在数百种大肠杆菌菌株中是相同的，这表明BamAEcoli和CdiAEC 93在自我-非自我辨别中发挥作用。接触依赖性生长抑制（CDI）系统广泛存在于革兰氏阴性菌中，使它们能够与邻近的细菌细胞结合并递送抑制细胞生长的蛋白质毒素。在这项研究中，我们测试了CDI在种间竞争中的作用，使用肠道分离大肠杆菌EC 93作为抑制剂细胞模型。虽然E. coliEC 93对不同的E.大肠杆菌菌株，来自肠道的其他细菌物种对CDI完全耐药。我们表明，耐药性是由于CDI受体的微小变化导致的，这些变化阻止了其他物种被识别为靶细胞。因此，CDI受体相互作用提供了一种机制，通过这种机制，细菌可以将同胞和其他近亲（自身）与更远的亲戚或其他细菌物种（非自身）区分开来。我们的研究结果提供了一种可能的方法，通过这种方法，抗菌剂可以通过使用特定的受体“邮政编码”来针对一种或仅几种相关的细菌病原体。
Bacteria that express contact-dependent growth inhibition (CDI) systems outcompete siblings that lack immunity, suggesting that CDI mediates intercellular competition. To further explore the role of CDI in competition, we determined the target cell range of the CDIEC93 system from Escherichia coli EC93. The CdiAEC93 effector protein recognizes the widely conserved BamA protein as a receptor, yet E. coli EC93 does not inhibit other enterobacterial species. The predicted membrane topology of BamA indicates that three of its extracellular loops vary considerably between species, suggesting that loop heterogeneity may control CDI specificity. Consistent with this hypothesis, other enterobacteria are sensitized to CDIEC93 upon the expression of E. coli bamA and E. coli cells become CDIEC93 resistant when bamA is replaced with alleles from other species. Our data indicate that BamA loops 6 and 7 form the CdiAEC93-binding epitope and their variation between species restricts CDIEC93 target cell selection. Although BamA loops 6 and 7 vary dramatically between species, these regions are identical in hundreds of E. coli strains, suggesting that BamAEcoli and CdiAEC93 play a role in self-nonself discrimination. Contact-dependent growth inhibition (CDI) systems are widespread among Gram-negative bacteria, enabling them to bind to neighboring bacterial cells and deliver protein toxins that inhibit cell growth. In this study, we tested the role of CDI in interspecies competition using intestinal isolate Escherichia coli EC93 as an inhibitor cell model. Although E. coli EC93 inhibits different E. coli strains, other bacterial species from the intestine are completely resistant to CDI. We show that resistance is due to small variations in the CDI receptor that prevent other species from being recognized as target cells. CDI receptor interactions thus provide a mechanism by which bacteria can distinguish siblings and other close relatives (self) from more distant relatives or other species of bacteria (nonself). Our results provide a possible means by which antimicrobials could be directed to one or only a few related bacterial pathogens by using a specific receptor “zip code.”