Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, California, USA.
mBio. 2013 Jul 23;4(4):e00480-13. doi: 10.1128/mBio.00480-13.
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."
表达接触依赖性生长抑制 (CDI) 系统的细菌会与缺乏免疫的兄弟姐妹竞争，这表明 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 EC93 的 CDIEC93 系统的靶细胞范围。CdiAEC93 效应蛋白将广泛保守的 BamA 蛋白识别为受体，但大肠杆菌 EC93 不会抑制其他肠杆菌物种。BamA 的预测膜拓扑结构表明，其三个细胞外环在物种之间差异很大，这表明环异质性可能控制 CDI 的特异性。与该假设一致，当在其他物种的 BamA 表达时，其他肠杆菌对 CDIEC93 敏感，并且当 BamA 被来自其他物种的等位基因取代时，大肠杆菌细胞对 CDIEC93 具有抗性。我们的数据表明，BamA 环 6 和 7 形成 CdiAEC93 结合表位，它们在物种之间的差异限制了 CDIEC93 的靶细胞选择。尽管 BamA 环 6 和 7 在物种之间差异很大，但这些区域在数百个大肠杆菌菌株中是相同的，这表明 BamAecoli 和 CdiAEC93 在自我非自我识别中发挥作用。
接触依赖性生长抑制 (CDI) 系统在革兰氏阴性菌中广泛存在，使它们能够与邻近的细菌细胞结合并传递抑制细胞生长的蛋白毒素。在这项研究中，我们使用肠道分离株大肠杆菌 EC93 作为抑制剂细胞模型，测试了 CDI 在种间竞争中的作用。尽管大肠杆菌 EC93 抑制不同的大肠杆菌菌株，但肠道中的其他细菌物种完全对 CDI 具有抗性。我们表明，这种抗性是由于 CDI 受体的微小变化所致，这些变化阻止了其他物种被识别为靶细胞。CDI 受体相互作用因此提供了一种机制，通过该机制，细菌可以区分兄弟姐妹和其他近亲（自我）与更远亲或其他细菌物种（非自我）。我们的结果提供了一种可能的方法，通过使用特定的受体“邮政编码”，可以将抗生素靶向一种或仅几种相关的细菌病原体。
