THE CELL CYCLE-SPECIFIC GROWTH-INHIBITORY FACTOR PRODUCED BY ACTINOBACILLUS-ACTINOMYCETEMCOMITANS IS A CYTOLETHAL DISTENDING TOXIN

Actinobacillus actinomycetemcomitans has been shown to produce a solub le cytotoxic factor(s) distinct from leukotoxin. We hare identified in A. actinomycetemcomitans Y4 a cluster of genes encoding a cytolethal distending toxin (CDT), This new member of the CDT family is similar t o the CDT produced by Haemophilus ducreyi. The CDT from A. actinomycet emcomitans was produced in Escherichia coli and was able to induce cel l distension, growth arrest in G(2)/M phase, nucleus swelling, and chr omatin fragmentation in HeLa cells. The three proteins, CDTA, -B and - C, encoded by the cdt locus were all required for toxin activity. Anti serum raised against recombinant CDTC completely inhibited the cytotox ic 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 supe rnatant and cell homogenate fractions of A. actinomycetemcomitans Y4, This CDT is a new putative virulence factor of A. actinomycetemcomitan s and may play a role in the pathogenesis of periodontal diseases.