The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thelestam, M.
Right arrow Articles by Frisan, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thelestam, M.
Right arrow Articles by Frisan, T.
The Journal of Immunology, 2004, 172: 5813.
Copyright © 2004 by The American Association of Immunologists

LETTERS TO THE EDITOR

A. actinomycetemcomitans Cytolethal Distending Toxin

Monica Thelestam and Teresa Frisan

Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden

Recently The JI published an interesting article by Shenker et al. (1) concerning the A. actinomycetemcomitans cytolethal distending toxin. However, we are concerned that readers not familiar with this family of bacterial toxins might be misled.

Our major criticism concerns two sentences on p. 417: "At this point it is premature to speculate as to whether the toxin simply acts at the cell surface to trigger a signal transduction cascade or enters the cell and interacts with specific subcellular targets. Clearly, further investigation is required to identify the cellular target(s) and molecular events by which Cdts induce cell cycle arrest."

We would like to draw attention to the following facts. The B subunit of CDT (CdtB) has DNase activity (2, 3), and all cytotoxic effects are abolished when residues responsible for the DNase activity are mutated. CDT induces DNA double strand breaks in target cells. This was shown in yeast cells transfected with the CdtB gene (4) and in mammalian cells naturally intoxicated by extracellular treatment with the toxin (5). Thus, the subcellular target of CDT is already known to be DNA.

Microinjection of CdtB is sufficient to induce intoxication (3, 6), implying that the toxin acts from inside the cell. Moreover, all cellular effects are blocked if the toxin is prevented from being endocytosed (7). Thus, the putative transmembrane signaling by cell surface-bound CDT has already been rejected.

With this letter we want to give The JI readers a broader vision of the CDT field as it is known in early 2004. We agree with Shenker et al. that there are still several unanswered questions, but the current knowledge is not as limited as they report.

References

  1. Shenker, B. J., D. Besack, T. McKay, L. Pankoski, A. Zekavat, D. R. Demuth. 2004. Actinobacillus actinomycetemcomitans cytolethal distending toxin (Cdt): evidence that the holotoxin is composed of three subunits: CdtA, CdtB, and CdtC. J. Immunol. 172:410.[Abstract/Free Full Text]
  2. Elwell, C. A., L. A. Dreyfus. 2000. DNase I homologous residues in CdtB are critical for cytolethal distending toxin-mediated cell cycle arrest. Mol. Microbiol. 37:952.[Medline]
  3. Lara-Tejero, M., J. E. Galan. 2000. A bacterial toxin that controls cell cycle progression as a deoxyribonuclease I-like protein. Science 290:354.[Abstract/Free Full Text]
  4. Hassane, D. C., R. B. Lee, M. D. Mendenhall, C. L. Pickett. 2001. Cytolethal distending toxin demonstrates genotoxic activity in a yeast model. Infect. Immun. 69:5752.[Abstract/Free Full Text]
  5. Frisan, T., X. Cortes-Bratti, E. Chaves-Olarte, B. Stenerlöw, M. Thelestam. 2003. The Haemophilus ducreyi cytolethal distending toxin induces DNA double strand breaks and promotes ATM-dependent activation of RhoA. Cell. Micro. 5:695.
  6. Elwell, C., K. Chao, K. Patel, L. Dreyfus. 2001. Escherichia coli CdtB mediates cytolethal distending toxin cell cycle arrest. Infect. Immun. 69:3418.[Abstract/Free Full Text]
  7. Cortes-Bratti, X., E. Chaves-Olarte, T. Lagergård, M. Thelestam. 2000. Cellular internalization of cytolethal distending toxin from Haemophilus ducreyi. Infect. Immun. 68:6903.[Abstract/Free Full Text]




This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thelestam, M.
Right arrow Articles by Frisan, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thelestam, M.
Right arrow Articles by Frisan, T.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS