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Infection and Immunity, July 2001, p. 4358-4365, Vol. 69, No. 7
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.7.4358-4365.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
CdtA, CdtB, and CdtC Form a Tripartite Complex That
Is Required for Cytolethal Distending Toxin Activity
María
Lara-Tejero and
Jorge E.
Galán*
Section of Microbial Pathogenesis, Boyer
Center for Molecular Medicine, Yale School of Medicine, New Haven,
Connecticut 06536
Received 1 February 2001/Returned for modification 28 March
2001/Accepted 9 April 2001
Campylobacter jejuni encodes a cytolethal distending
toxin (CDT) that causes cells to arrest in the G2/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 G2/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.
*
Corresponding author. Mailing address: Section of
Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale
University School of Medicine, 295 Congress Ave., Rm. 354F, P.O. Box
9812, New Haven, CT 06536-9812. Phone: (203) 737-2404. Fax: (203)
737-2630. E-mail: jorge.galan{at}yale.edu.
Infection and Immunity, July 2001, p. 4358-4365, Vol. 69, No. 7
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.7.4358-4365.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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