CdtA, CdtB, and CdtC form a tripartite complex that is required for cytolethal distending toxin activity

Campylobacter jejuni encodes a cytolethal distending toxin (CDT) that cause s 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. CD T activity requires the function of three genes: cdtA, cdtB, and cdtC, Rece nt studies have established that CdtB is the active subunit of CDT, exertin g its effect as a nuclease that damages the DNA and triggers cell cycle arr est. Microinjection of CdtB into target cells led to G(2)/M arrest and cyto plasmic distention, in a manner indistinguishable from that caused by CDT t reatment. 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 a ctivity. 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 ric in-related toxins. We therefore proposed that CDT is a tripartite toxin com posed of CdtB as the enzymatically active subunit and of CdtA and CdtC as t he heterodimeric B subunit required for the delivery of CdtB.