The cell cycle-specific growth-inhibitory factor produced by Actinobacillus actinomycetemcomitans is a cytolethal distending toxin.
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.
Sugai
M
M
Department of Microbiology, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan. sugai@ipc.hiroshima-u.ac.jp/
Kawamoto
T
T
Pérès
S Y
SY
Ueno
Y
Y
Komatsuzawa
H
H
Fujiwara
T
T
Kurihara
H
H
Suginaka
H
H
Oswald
E
E
D016976:Aggregatibacter actinomycetemcomitans / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000235:genetics / Q000494:pharmacology*; D001483:Base Sequence; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D016195:G2 Phase / Q000187:drug effects; D005798:Genes, Bacterial; D006131:Growth Inhibitors / Q000235:genetics / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D008969:Molecular Sequence Data; D005810:Multigene Family; D011994:Recombinant Proteins / Q000494:pharmacology; D015183:Restriction Mapping
D001427:Bacterial Toxins; D006131:Growth Inhibitors; D011994:Recombinant Proteins; C067044:cytolethal distending toxin