Cytolethal distending toxin

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Cytolethal distending toxin subunit A
other names

Cdt

Mass / length primary structure 268 amino acids , 29,919 Da
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Cytolethal distending toxin subunit B
Mass / length primary structure 265 amino acids , 28,973 Da
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Cytolethal distending toxin subunit C.
Mass / length primary structure 189 amino acids , 21,127 Da
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Cytolethal distending toxin (Cdt, in German roughly ' cell-fatal swelling toxin ') is a protein from various Gram-negative bacteria and a microbial exotoxin .

properties

Cdt is a heterotrimeric protein and consists of the subunits CdtA, CdtB and CdtC. It is one of the AB toxins . The subunits CdtA and CdtC mediate binding to eukaryotic cells . They are probably bound to cholesterol , N-glycans or glycosphingolipids . After being absorbed into cells, Cdt is imported into the cell nucleus . The binding subunits A and C are relatively poorly conserved , with a match of sometimes less than 30% in the DNA sequence between the Cdt-producing bacterial species. Accordingly, the molecular weights are comparatively variable, for A between 23 and 30 kilodaltons and for C between 19 and 21 Kda. Both A and C contain a lectin domain. In contrast to all other Cdt-producing bacteria, S. enterica serotype Typhi does not use CdtA and C, but the A and B subunits of the pertussis-like toxin , PltA and PltB. There is probably more than one binding mechanism in the different types of bacteria, with some binding to lipid rafts , especially to the cholesterol they contain.

The CdtB subunit has DNase activity and is homologous to DNase I . As a result, Cdt has a genotoxic effect . Cdt is palmitoylated .

Cdt causes swelling of the cells , arrest of the cell cycle in the G2 / M phase, swelling of the cell nucleus and fragmentation of chromatin and ultimately apoptosis in various mammalian cell types. Apoptosis occurs primarily in lymphocytes . The cell cycle arrest is caused by DNA damage (double strand break) and ATM . There is also an ADP-ribosyltransferase activity.

Occurrence

Cdt are produced by gram-negative bacteria of the γ and ε classes of the Proteobacteria . Medically important Cdt-producing bacteria are Haemophilus ducreyi , Aggregatibacter actinomycetemcomitans , Escherichia coli , Shigella dysenteriae , Salmonella enterica serotype Typhi, Campylobacter upsaliensis , Campylobacter jejuni .

Web links

Individual evidence

  1. ^ A b A. Eshraghi, FJ Maldonado-Arocho, A. Gargi, MM Cardwell, MG Prouty, SR Blanke, KA Bradley: Cytolethal distending toxin family members are differentially affected by alterations in host glycans and membrane cholesterol. In: The Journal of biological chemistry. Volume 285, Number 24, June 2010, pp. 18199-18207, doi : 10.1074 / jbc.M110.112912 , PMID 20385557 , PMC 2881744 (free full text).
  2. ↑ JM DiRienzo: Uptake and processing of the cytolethal distending toxin by mammalian cells. In: Toxins. Volume 6, number 11, October 2014, pp. 3098-3116, doi : 10.3390 / toxins6113098 , PMID 25365527 , PMC 4247254 (free full text).
  3. ↑ a b Lina Guerra, Ximena Cortes Bratti, Riccardo Guidi, Teresa Frisan: The Biology of the Cytolethal distending toxin. In: Toxins. 3, 2011, p. 172, doi : 10.3390 / toxins3030172 .
  4. ↑ a b c d R. N. Jinadasa, SE Bloom, RS Weiss, GE Duhamel: Cytolethal distending toxin: a conserved bacterial genotoxin that blocks cell cycle progression, leading to apoptosis of a broad range of mammalian cell lineages. In: Microbiology. Volume 157, Pt 7 July 2011, pp. 1851-1875, doi : 10.1099 / mic.0.049536-0 , PMID 21565933 , PMC 3167888 (free full text).
  5. ↑ D. Nesić, Y. Hsu, CE Stebbins: Assembly and function of a bacterial genotoxin. In: Nature. Volume 429, number 6990, May 2004, pp. 429-433, doi : 10.1038 / nature02532 , PMID 15164065 .
  6. ↑ Stefania Spanò, Juan E. Ugalde, Jorge E. Galán: Delivery of a Salmonella Typhi Exotoxin from a Host Intracellular Compartment. In: Cell Host & Microbe. 3, 2008, p. 30, doi : 10.1016 / j.chom.2007.11.001 .
  7. ↑ K. Boesze-Battaglia, D. Alexander, M. Dlakić, BJ Shenker: A Journey of Cytolethal Distending Toxins through Cell Membranes. In: Frontiers in cellular and infection microbiology. Volume 6, 2016, p. 81, doi : 10.3389 / fcimb.2016.00081 , PMID 27559534 , PMC 4978709 (free full text).
  8. ↑ CK Lai, YA Chen, CJ Lin, HJ Lin, MC Kao, MZ Huang, YH Lin, C. Chiang-Ni, CJ Chen, UG Lo, LC Lin, H. Lin, JT Hsieh, CH Lai: Molecular Mechanisms and Potential Clinical Applications of Campylobacter jejuni Cytolethal Distending Toxin. In: Frontiers in cellular and infection microbiology. Volume 6, 2016, p. 9, doi : 10.3389 / fcimb.2016.00009 , PMID 26904508 , PMC 4746238 (free full text).
  9. ↑ Cherilyn A. Elwell, Lawrence A. Dreyfus: DNase I homologous residues in CdtB are critical for cytolethal distending toxin-mediated cell cycle arrest. In: Molecular Microbiology. 37, 2000, p. 952, doi : 10.1046 / j.1365-2958.2000.02070.x .
  10. ↑ a b B. J. Shenker, M. Dlakic, LP Walker, D. Besack, E. Jaffe, E. LaBelle, 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. In: The Journal of Immunology. 178, 2007, p. 5099, doi : 10.4049 / jimmunol.178.8.5099 .
  11. ↑ T. Faïs, J. Delmas, A. Serres, R. Bonnet, G. Dalmasso: Impact of CDT Toxin on Human Diseases. In: Toxins. Volume 8, number 7, 07 2016, p., Doi : 10.3390 / toxins8070220 , PMID 27429000 , PMC 4963852 (free full text).
  12. ^ R. Miller, M. Wiedmann: Dynamic Duo-The Salmonella Cytolethal Distending Toxin Combines ADP-Ribosyltransferase and Nuclease Activities in a Novel Form of the Cytolethal Distending Toxin. In: Toxins. Volume 8, number 5, 04 2016, p., Doi : 10.3390 / toxins8050121 , PMID 27120620 , PMC 4885037 (free full text).