Hayes Christopher S, Koskiniemi Sanna, Ruhe Zachary C, Poole Stephen J, Low David A
Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, California 93106-9625.
Cold Spring Harb Perspect Med. 2014 Feb 1;4(2):a010025. doi: 10.1101/cshperspect.a010025.
Bacterial contact-dependent growth inhibition (CDI) is mediated by the CdiA/CdiB family of two-partner secretion proteins. CDI(+) cells bind to susceptible target bacteria and deliver a toxic effector domain derived from the carboxyl terminus of CdiA (CdiA-CT). More than 60 distinct CdiA-CT sequence types have been identified, and all CDI toxins characterized thus far display RNase, DNase, or pore-forming activities. CDI systems also encode CdiI immunity proteins, which specifically bind and inactivate cognate CdiA-CT toxins to prevent autoinhibition. CDI activity appears to be limited to target cells of the same species, suggesting that these systems play a role in competition between closely related bacteria. Recent work on the CDI system from uropathogenic Escherichia coli (UPEC 536) has revealed that its CdiA-CT toxin binds tightly to a cysteine biosynthetic enzyme (CysK) in the cytoplasm of target cells. The unanticipated complexity in the UPEC CDI pathway raises the possibility that these systems perform other functions in addition to growth inhibition. Finally, we propose that the phenomenon of CDI is more widespread than previously appreciated. Rhs (rearrangement hotspot) systems encode toxin-immunity pairs, some of which share significant sequence identity with CdiA-CT/CdiI proteins. A number of recent observations suggest that Rhs proteins mediate a distinct form of CDI.
细菌接触依赖性生长抑制（CDI）由双组分分泌蛋白的CdiA/CdiB家族介导。CDI（+）细胞与易感靶细菌结合，并传递源自CdiA羧基末端（CdiA-CT）的毒性效应结构域。已鉴定出60多种不同的CdiA-CT序列类型，并且迄今为止表征的所有CDI毒素均显示出核糖核酸酶、脱氧核糖核酸酶或成孔活性。CDI系统还编码CdiI免疫蛋白，其特异性结合并灭活同源CdiA-CT毒素以防止自我抑制。CDI活性似乎仅限于同一物种的靶细胞，这表明这些系统在密切相关细菌之间的竞争中起作用。最近关于尿路致病性大肠杆菌（UPEC 536）的CDI系统的研究表明，其CdiA-CT毒素紧密结合靶细胞胞质中的一种半胱氨酸生物合成酶（CysK）。UPEC CDI途径中意想不到的复杂性增加了这些系统除生长抑制外还执行其他功能的可能性。最后，我们提出CDI现象比以前认识到的更为普遍。Rhs（重排热点）系统编码毒素-免疫对，其中一些与CdiA-CT/CdiI蛋白具有显著的序列同一性。最近的一些观察结果表明，Rhs蛋白介导一种独特形式的CDI。
