Lara-Tejero M, Galán J E
Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale School of Medicine, New Haven, Connecticut 06536, USA.
Infect Immun. 2001 Jul;69(7):4358-65. doi: 10.1128/IAI.69.7.4358-4365.2001.
Campylobacter jejuni encodes a cytolethal distending toxin (CDT) that causes cells to arrest in the G(2)/M transition phase of the cell cycle. Highly related toxins are also produced by other important bacterial pathogens. CDT activity requires the function of three genes: cdtA, cdtB, and cdtC. Recent studies have established that CdtB is the active subunit of CDT, exerting its effect as a nuclease that damages the DNA and triggers cell cycle arrest. Microinjection of CdtB into target cells led to G(2)/M arrest and cytoplasmic distention, in a manner indistinguishable from that caused by CDT treatment. Despite this progress, nothing is known about the composition of the CDT holotoxin or the function of CdtA and CdtC. We show here that, when applied individually, purified CdtA, CdtB, or CdtC does not exhibit toxic activity. In contrast, CdtA, CdtB, and CdtC when combined, interact with one another to form an active tripartite holotoxin that exhibits full cellular toxicity. CdtA has a domain that shares similarity with the B chain of ricin-related toxins. We therefore proposed that CDT is a tripartite toxin composed of CdtB as the enzymatically active subunit and of CdtA and CdtC as the heterodimeric B subunit required for the delivery of CdtB.
空肠弯曲菌编码一种细胞致死性扩张毒素（CDT），该毒素可使细胞停滞在细胞周期的G(2)/M转换期。其他重要的细菌病原体也会产生高度相关的毒素。CDT的活性需要三个基因的功能：cdtA、cdtB和cdtC。最近的研究证实，CdtB是CDT的活性亚基，作为一种核酸酶发挥作用，破坏DNA并触发细胞周期停滞。将CdtB显微注射到靶细胞中会导致G(2)/M停滞和细胞质扩张，其方式与CDT处理引起的情况无法区分。尽管取得了这一进展，但对于CDT全毒素的组成或CdtA和CdtC的功能仍一无所知。我们在此表明，单独应用时，纯化的CdtA、CdtB或CdtC均不表现出毒性活性。相反，CdtA、CdtB和CdtC组合时会相互作用，形成一种具有活性的三方全毒素，表现出完全的细胞毒性。CdtA有一个与蓖麻毒素相关毒素的B链具有相似性的结构域。因此，我们提出CDT是一种三方毒素，由作为酶活性亚基的CdtB以及作为CdtB传递所需异二聚体B亚基的CdtA和CdtC组成。
