| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Pathology and
Biochemistry, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104
We have previously shown that Actinobacillus
actinomycetecomitans produces an immunosuppressive factor (ISF)
capable of impairing human lymphocyte function by perturbing cell cycle
progression. We now report that ISF is the product of the
cdtB gene, one of three genes encoding the family of
cytolethal distending toxins (Cdt). The ISF polypeptide exhibits 
95%
identity with Hemophilus ducreyi CdtB protein and 
60%
homology with Escherichia coli or Campylobacter
jejuni CdtB. Pretreatment of PHA-activated lymphocytes with
5–25 ng ISF results in G2 arrest of CD4+ and
CD8+ T cells. Similarly, treatment of HeLa cells results in
G2 arrest and cell elongation and distension. However,
lymphocytes are at least 5 times more sensitive to ISF than HeLa cells
and do not undergo the elongation and distension that characterizes
interactions of Cdts with cell lines. ISF-treated lymphocytes express
normal cyclin A and B1 levels, but contain reduced levels of cell
cycle-dependent kinase-1 (Cdk1). Additionally, the majority of Cdk1 is
in the hyperphosphorylated, inactive, form. In contrast, PHA-induced
G2 cells contain elevated levels of the hypophosphorylated,
active Cdk1. Failure of ISF-treated cells to dephosphorylate Cdk1 is
not associated with decreased availability of Cdc25. These studies
suggest that the CdtB protein alone is capable of inducing
G2 arrest in lymphocytes and cell cycle arrest, elongation,
and distension of HeLa cells. Our studies also suggest that lymphocytes
may be primary targets for A. actinomycetemcomitans CdtB
(ISF) and possibly for other Cdt family members as well. Thus, Cdts may
function to impair host immunity and contribute to the pathogenesis of
disease associated with Cdt-producing organisms.
This article has been cited by other articles:
|
|
 |
|
  M. Handfield, H.V. Baker, and R.J. Lamont Beyond Good and Evil in the Oral Cavity: Insights into Host-Microbe Relationships Derived from Transcriptional Profiling of Gingival Cells J. Dent. Res., March 1, 2008; 87(3): 203 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Schaeffer, M. L. Schmidt, and D. R. Demuth Induction of Aggregatibacter actinomycetemcomitans leukotoxin expression by IS1301 and orfA Microbiology, February 1, 2008; 154(2): 528 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Shenker, M. Dlakic, L. P. Walker, D. Besack, E. Jaffe, E. LaBelle, and K. Boesze-Battaglia A Novel Mode of Action for a Microbial-Derived Immunotoxin: The Cytolethal Distending Toxin Subunit B Exhibits Phosphatidylinositol 3,4,5-Triphosphate Phosphatase Activity J. Immunol., April 15, 2007; 178(8): 5099 - 5108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kitagawa, H. Hoshida, and R. Akada Genome-Wide Analysis of Cellular Response to Bacterial Genotoxin CdtB in Yeast Infect. Immun., March 1, 2007; 75(3): 1393 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Cao, A. Volgina, J. Korostoff, and J. M. DiRienzo Role of Intrachain Disulfides in the Activities of the CdtA and CdtC Subunits of the Cytolethal Distending Toxin of Actinobacillus actinomycetemcomitans Infect. Immun., September 1, 2006; 74(9): 4990 - 5002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yamada, J. Komoto, K. Saiki, K. Konishi, and F. Takusagawa Variation of loop sequence alters stability of cytolethal distending toxin (CDT): Crystal structure of CDT from Actinobacillus actinomycetemcomitans Protein Sci., February 1, 2006; 15(2): 362 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Pouniotis, O. Proudfoot, V. Bogdanoska, K. Scalzo, S. Kovacevic, R. L. Coppel, and M. Plebanski Selectively Impaired CD8+ but Not CD4+ T Cell Cycle Arrest during Priming as a Consequence of Dendritic Cell Interaction with Plasmodium-Infected Red Cells J. Immunol., September 15, 2005; 175(6): 3525 - 3533. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Kang, J. Korostoff, A. Volgina, W. Grzesik, and J. M DiRienzo Differential effect of the cytolethal distending toxin of Actinobacillus actinomycetemcomitans on co-cultures of human oral cells J. Med. Microbiol., August 1, 2005; 54(8): 785 - 794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ge, Y. Feng, M. T. Whary, P. R. Nambiar, S. Xu, V. Ng, N. S. Taylor, and J. G. Fox Cytolethal Distending Toxin Is Essential for Helicobacter hepaticus Colonization in Outbred Swiss Webster Mice Infect. Immun., June 1, 2005; 73(6): 3559 - 3567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Akifusa, W. Heywood, S. P. Nair, G. Stenbeck, and B. Henderson Mechanism of internalization of the cytolethal distending toxin of Actinobacillus actinomycetemcomitans Microbiology, May 1, 2005; 151(5): 1395 - 1402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Heywood, B. Henderson, and S. P Nair Cytolethal distending toxin: creating a gap in the cell cycle J. Med. Microbiol., March 1, 2005; 54(3): 207 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Shenker, D. Besack, T. McKay, L. Pankoski, A. Zekavat, and D. R. Demuth Induction of Cell Cycle Arrest in Lymphocytes by Actinobacillus actinomycetemcomitans Cytolethal Distending Toxin Requires Three Subunits for Maximum Activity J. Immunol., February 15, 2005; 174(4): 2228 - 2234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Dassanayake, Y. Zhou, S. Hinkley, C. J. Stryker, G. Plauche, J. T. Borda, K. Sestak, and G. E. Duhamel Characterization of Cytolethal Distending Toxin of Campylobacter Species Isolated from Captive Macaque Monkeys J. Clin. Microbiol., February 1, 2005; 43(2): 641 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. N. Belibasakis, A. Johansson, Y. Wang, C. Chen, S. Kalfas, and U. H. Lerner The Cytolethal Distending Toxin Induces Receptor Activator of NF-{kappa}B Ligand Expression in Human Gingival Fibroblasts and Periodontal Ligament Cells Infect. Immun., January 1, 2005; 73(1): 342 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ohara, E. Oswald, and M. Sugai Cytolethal Distending Toxin: A Bacterial Bullet Targeted to Nucleus J. Biochem., October 1, 2004; 136(4): 409 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Saiki, T. Gomi, and K. Konishi Deletion and Purification Studies to Elucidate the Structure of the Actinobacillus actinomycetemcomitans Cytolethal Distending Toxin J. Biochem., September 1, 2004; 136(3): 335 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Haghjoo and J. E. Galan Salmonella typhi encodes a functional cytolethal distending toxin that is delivered into host cells by a bacterial-internalization pathway PNAS, March 30, 2004; 101(13): 4614 - 4619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ohara, T. Hayashi, Y. Kusunoki, M. Miyauchi, T. Takata, and M. Sugai Caspase-2 and Caspase-7 Are Involved in Cytolethal Distending Toxin-Induced Apoptosis in Jurkat and MOLT-4 T-Cell Lines Infect. Immun., February 1, 2004; 72(2): 871 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Shenker, D. Besack, T. McKay, L. Pankoski, A. Zekavat, and D. R. Demuth Actinobacillus actinomycetemcomitans Cytolethal Distending Toxin (Cdt): Evidence That the Holotoxin Is Composed of Three Subunits: CdtA, CdtB, and CdtC J. Immunol., January 1, 2004; 172(1): 410 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mitchell, L. Gao, and D. R. Demuth Positive and Negative cis-Acting Regulatory Sequences Control Expression of Leukotoxin in Actinobacillus actinomycetemcomitans 652 Infect. Immun., October 1, 2003; 71(10): 5640 - 5649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Yamano, M. Ohara, S. Nishikubo, T. Fujiwara, T. Kawamoto, Y. Ueno, H. Komatsuzawa, K. Okuda, H. Kurihara, H. Suginaka, et al. Prevalence of Cytolethal Distending Toxin Production in Periodontopathogenic Bacteria J. Clin. Microbiol., April 1, 2003; 41(4): 1391 - 1398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. Fong, L. Gao, and D. R. Demuth luxS and arcB Control Aerobic Growth of Actinobacillus actinomycetemcomitans under Iron Limitation Infect. Immun., January 1, 2003; 71(1): 298 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Hassane, R. B. Lee, and C. L. Pickett Campylobacter jejuni Cytolethal Distending Toxin Promotes DNA Repair Responses in Normal Human Cells Infect. Immun., January 1, 2003; 71(1): 541 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. HENDERSON, M. WILSON, L. SHARP, and J. M. WARD Actinobacillus actinomycetemcomitans J. Med. Microbiol., December 1, 2002; 51(12): 1013 - 1020. [Full Text] [PDF]
|
|
|
|
|
|
T. Sato, T. Koseki, K. Yamato, K. Saiki, K. Konishi, M. Yoshikawa, I. Ishikawa, and T. Nishihara p53-Independent Expression of p21CIP1/WAF1 in Plasmacytic Cells during G2 Cell Cycle Arrest Induced by Actinobacillus actinomycetemcomitans Cytolethal Distending Toxin Infect. Immun., February 1, 2002; 70(2): 528 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. Fong, W. O. Chung, R. J. Lamont, and D. R. Demuth Intra- and Interspecies Regulation of Gene Expression by Actinobacillus actinomycetemcomitans LuxS Infect. Immun., December 1, 2001; 69(12): 7625 - 7634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Lewis, M. K. Stevens, J. L. Latimer, C. K. Ward, K. Deng, R. Blick, S. R. Lumbley, C. A. Ison, and E. J. Hansen Characterization of Haemophilus ducreyi cdtA, cdtB, and cdtC Mutants in In Vitro and In Vivo Systems Infect. Immun., September 1, 2001; 69(9): 5626 - 5634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Hassane, R. B. Lee, M. D. Mendenhall, and C. L. Pickett Cytolethal Distending Toxin Demonstrates Genotoxic Activity in a Yeast Model Infect. Immun., September 1, 2001; 69(9): 5752 - 5759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Akifusa, S. Poole, J. Lewthwaite, B. Henderson, and S. P. Nair Recombinant Actinobacillus actinomycetemcomitans Cytolethal Distending Toxin Proteins Are Required To Interact To Inhibit Human Cell Cycle Progression and To Stimulate Human Leukocyte Cytokine Synthesis Infect. Immun., September 1, 2001; 69(9): 5925 - 5930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lara-Tejero and J. E. Galan CdtA, CdtB, and CdtC Form a Tripartite Complex That Is Required for Cytolethal Distending Toxin Activity Infect. Immun., July 1, 2001; 69(7): 4358 - 4365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Shenker, R. H. Hoffmaster, A. Zekavat, N. Yamaguchi, E. T. Lally, and D. R. Demuth Induction of Apoptosis in Human T Cells by Actinobacillus actinomycetemcomitans Cytolethal Distending Toxin Is a Consequence of G2 Arrest of the Cell Cycle J. Immunol., July 1, 2001; 167(1): 435 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Elwell, K. Chao, K. Patel, and L. Dreyfus Escherichia coli CdtB Mediates Cytolethal Distending Toxin Cell Cycle Arrest Infect. Immun., May 1, 2001; 69(5): 3418 - 3422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mooney, M. Clyne, T. Curran, D. Doherty, B. Kilmartin, and B. Bourke Campylobacter upsaliensis exerts a cytolethal distending toxin effect on HeLa cells and T lymphocytes Microbiology, March 1, 2001; 147(3): 735 - 743. [Abstract] [Full Text]
|
|
|
|
|
|
T. E. Hickey, A. L. McVeigh, D. A. Scott, R. E. Michielutti, A. Bixby, S. A. Carroll, A. L. Bourgeois, and P. Guerry Campylobacter jejuni Cytolethal Distending Toxin Mediates Release of Interleukin-8 from Intestinal Epithelial Cells Infect. Immun., December 1, 2000; 68(12): 6535 - 6541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Cortes-Bratti, E. Chaves-Olarte, T. Lagergard, and M. Thelestam Cellular Internalization of Cytolethal Distending Toxin from Haemophilus ducreyi Infect. Immun., December 1, 2000; 68(12): 6903 - 6911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Kachlany, P. J. Planet, M. K. Bhattacharjee, E. Kollia, R. DeSalle, D. H. Fine, and D. H. Figurski Nonspecific Adherence by Actinobacillus actinomycetemcomitans Requires Genes Widespread in Bacteria and Archaea J. Bacteriol., November 1, 2000; 182(21): 6169 - 6176. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Lara-Tejero and J. E. Galán A Bacterial Toxin That Controls Cell Cycle Progression as a Deoxyribonuclease I-Like Protein Science, October 13, 2000; 290(5490): 354 - 357. [Abstract] [Full Text]
|
|
|
|
|
|
B. J. Shenker, R. H. Hoffmaster, T. L. McKay, and D. R. Demuth Expression of the Cytolethal Distending Toxin (Cdt) Operon in Actinobacillus actinomycetemcomitans: Evidence That the CdtB Protein Is Responsible for G2 Arrest of the Cell Cycle in Human T Cells J. Immunol., September 1, 2000; 165(5): 2612 - 2618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. PURDY, C.M. BUSWELL, A.E. HODGSON, K. McALPINE, I. HENDERSON, and S.A. LEACH Characterisation of cytolethal distending toxin (CDT) mutants of Campylobacter jejuni J. Med. Microbiol., May 1, 2000; 49(5): 473 - 479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Gelfanova, E. J. Hansen, and S. M. Spinola Cytolethal Distending Toxin of Haemophilus ducreyi Induces Apoptotic Death of Jurkat T Cells Infect. Immun., December 1, 1999; 67(12): 6394 - 6402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Cortes-Bratti, C. Karlsson, T. Lagergard, M. Thelestam, and T. Frisan The Haemophilus ducreyi Cytolethal Distending Toxin Induces Cell Cycle Arrest and Apoptosis via the DNA Damage Checkpoint Pathways J. Biol. Chem., February 9, 2001; 276(7): 5296 - 5302. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
