首次于5年前在大肠杆菌中发现的“依赖于接触的生长抑制” (CDI),是“细胞到细胞接触”用来抑制没有这一体系的细菌细胞生长的一个机制。CDI由“二伙伴”分泌蛋白CdiA 和 CdiB调控,一个小的免疫蛋白CdiI保护其不受自身抑制作用影响。
现在CDI中所涉及的一些相互作用已经搞清:CdiA的毒性被限制在该蛋白的羧基端(CdiA-CT)。对大肠杆菌其他菌种和细菌物种所做的搜索显示这个体系是广泛存在的,一系列细菌含有一个或多个CdiA同源染色体,其中有不同的CdiA-CT毒素序列。这些发现表明,CDI体系构成一个错综复杂的免疫网络,在环境中的细菌生长竞争中发挥一个重要功能。
英文摘要:
Nature doi:10.1038/nature09490
A widespread family of polymorphic contact-dependent toxin delivery systems in bacteria
Stephanie K. Aoki,Elie J. Diner,Claire t’Kint de Roodenbeke,Brandt R. Burgess,Stephen J. Poole,Bruce A. Braaten,Allison M. Jones,Julia S. Webb,Christopher S. Hayes,Peggy A. Cotter" David A. Low
Bacteria have developed mechanisms to communicate and compete with one another in diverse environments1. A new form of intercellular communication, contact-dependent growth inhibition (CDI), was discovered recently in Escherichia coli2. CDI is mediated by the CdiB/CdiA two-partner secretion (TPS) system. CdiB facilitates secretion of the CdiA ‘exoprotein’ onto the cell surface. An additional small immunity protein (CdiI) protects CDI+ cells from autoinhibition2, 3. The mechanisms by which CDI blocks cell growth and by which CdiI counteracts this growth arrest are unknown. Moreover, the existence of CDI activity in other bacteria has not been explored. Here we show that the CDI growth inhibitory activity resides within the carboxy-terminal region of CdiA (CdiA-CT), and that CdiI binds and inactivates cognate CdiA-CT, but not heterologous CdiA-CT. Bioinformatic and experimental analyses show that multiple bacterial species encode functional CDI systems with high sequence variability in the CdiA-CT and CdiI coding regions. CdiA-CT heterogeneity implies that a range of toxic activities are used during CDI. Indeed, CdiA-CTs from uropathogenic E.?coli and the plant pathogen Dickeya dadantii have different nuclease activities, each providing a distinct mechanism of growth inhibition. Finally, we show that bacteria lacking the CdiA-CT and CdiI coding regions are unable to compete with isogenic wild-type CDI+ cells both in laboratory media and on a eukaryotic host. Taken together, these results suggest that CDI systems constitute an intricate immunity network with an important function in bacterial competition.