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Infection and Immunity, October 1998, p. 5008-5019, Vol. 66, No. 10
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Cell Cycle-Specific Growth-Inhibitory Factor Produced by Actinobacillus actinomycetemcomitans Is a Cytolethal Distending Toxin

Motoyuki Sugai,1,* Toru Kawamoto,1,2 Sylvie Y. Pérès,3 Yoko Ueno,1 Hitoshi Komatsuzawa,1 Tamaki Fujiwara,1 Hidemi Kurihara,2 Hidekazu Suginaka,1 and Eric Oswald3

Department of Microbiology1 and Department of Periodontology and Endodontology,2 Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan, and Unité Associée INRA de Microbiologie Moléculaire, Ecole Nationale Vétérinaire de Toulouse, 31076 Toulouse Cedex, France3

Received 8 April 1998/Returned for modification 3 June 1998/Accepted 10 July 1998

Actinobacillus actinomycetemcomitans has been shown to produce a soluble cytotoxic factor(s) distinct from leukotoxin. We have identified in A. actinomycetemcomitans Y4 a cluster of genes encoding a cytolethal distending toxin (CDT). This new member of the CDT family is similar to the CDT produced by Haemophilus ducreyi. The CDT from A. actinomycetemcomitans was produced in Escherichia coli and was able to induce cell distension, growth arrest in G2/M phase, nucleus swelling, and chromatin fragmentation in HeLa cells. The three proteins, CDTA, -B and -C, encoded by the cdt locus were all required for toxin activity. Antiserum raised against recombinant CDTC completely inhibited the cytotoxic activity of culture supernatant and cell homogenate fractions of A. actinomycetemcomitans Y4. These results strongly suggest that the CDT is responsible for the cytotoxic activity present in the culture supernatant and cell homogenate fractions of A. actinomycetemcomitans Y4. This CDT is a new putative virulence factor of A. actinomycetemcomitans and may play a role in the pathogenesis of periodontal diseases.

* Corresponding author. Mailing address: Department of Microbiology, Hiroshima University School of Dentistry, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan. Phone: 81 82 257 5637. Fax: 81 82 257 5639. E-mail: sugai{at}ipc.hiroshima-u.ac.jp/.

Infection and Immunity, October 1998, p. 5008-5019, Vol. 66, No. 10
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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