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Infection and Immunity, March 1999, p. 1227-1237, Vol. 67, No. 3
Department of Microbiology, School of Dental
Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
19104-6002,1 and Department of
Microbiology, University of Texas Southwestern Medical Center,
Dallas, Texas 75235-90482
Received 26 October 1998/Returned for modification 4 December
1998/Accepted 15 December 1998
A genetic locus for a cytolethal distending toxin (CDT) was
identified in a polymorphic region of the chromosome of
Actinobacillus actinomycetemcomitans, a predominant oral
pathogen. The locus was comprised of three open reading frames (ORFs)
that had significant amino acid sequence similarity and more than 90%
sequence identity to the cdtABC genes of some pathogenic
Escherichia coli strains and Haemophilus
ducreyi, respectively. Sonic extracts from recombinant E. coli, containing the A. actinomycetemcomitans ORFs,
caused the distension and killing of Chinese hamster ovary cells
characteristic of a CDT. Monoclonal antibodies made reactive with the
CdtA, CdtB, and CdtC proteins of H. ducreyi recognized the
corresponding gene products from the recombinant strain. CDT-like
activities were no longer expressed by the recombinant strain when an
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Copyright © 1999, American Society for Microbiology. All rights reserved.
Identification of a Cytolethal Distending Toxin
Gene Locus and Features of a Virulence-Associated Region in
Actinobacillus actinomycetemcomitans
Kan-2 interposon was inserted into the cdtA and
cdtB genes. Expression of the CDT-like activities in
A. actinomycetemcomitans was strain specific. Naturally occurring expression-negative strains had large deletions within the
region of the cdt locus. The cdtABC genes were
flanked by an ORF (virulence plasmid protein), a partial ORF
(integrase), and DNA sequences (bacteriophage integration site)
characteristic of virulence-associated regions. These results provide
evidence for a functional CDT in a human oral pathogen.
*
Corresponding author. Mailing address: Department of
Microbiology, University of Pennsylvania School of Dental Medicine,
4001 Spruce St., Philadelphia, PA 19104-6002. Phone: (215) 898-6551. Fax: (215) 898-8385. E-mail: dirienzo{at}pobox.upenn.edu.
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