#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Cytolethal distending toxins


Authors: K. Čurová;  M. Kmeťová;  L. Siegfried
Authors‘ workplace: Ústav lekárskej a klinickej mikrobiológie UPJŠ LF a UN LP Košice
Published in: Epidemiol. Mikrobiol. Imunol. 63, 2014, č. 2, s. 134-139
Category: Review articles, original papers, case report

Overview

Cytolethal distending toxins (CDT) are intracellularly acting proteins which interfere with the eukaryotic cell cycle. They are produced by Gram-negative bacteria with affinity to mucocutaneous surfaces and could play a role in the pathogenesis of various mammalian diseases. The functional toxin is composed of three proteins: CdtB entering the nucleus and by its nuclease activity inducing nuclear fragmentation and chromatin disintegration, CdtA, and CdtC, the two latter being responsible for toxin attachment to the surface of the target cell. Cytotoxic effect of CDT leads to the cell cycle arrest before the cell enters mitosis and to further changes (cell distension and death, apoptosis) depending on the cell type. Thus, CDT may function as a virulence factor in pathogenic bacteria that produce it and thus may contribute to the initiation of certain diseases. Most important are inflammatory bowel diseases caused by intestinal bacteria, periodontitis with Aggregatibacter actinomycetemcomitans as the aetiologic agent and ulcus molle where Haemophilus ducreyi is the causative agent.

Keywords:
cytolethal distending toxin – CDT – virulence factor – Gram-negative bacteria


Sources

1. Johnson WM, Lior H. Production of Shiga toxin and a cytolethal distending toxin (CLDT) by serogroups of Shigella spp. FEMS Microbiol Lett, 1987;48:235–238.

2. Johnson WM, Lior H. A new heat-labile cytolethal distending toxin (CLDT) produced by Campylobacter spp. Microb Pathog, 1988;4:115–126.

3. Johnson WM, Lior H. A new heat-labile cytolethal distending toxin (CLDT) produced by Escherichia coli isolates from clinical material. Microb Pathog, 1988;4:103–113.

4. Jinadasa RN, Bloom SE, Weiss RS, Duhamel GE. Cytolethal distending toxin: a conserved bacterial genotoxin that blocks cell cycle progression, leading to apoptosis of a broad range of mammalian cell lineages. Microbiology, 2011;157:1851–1875.

5. Smith JL, Bayles DO. The contribution of cytolethal distending toxin to bacterial pathogenesis. Crit Rev Microbiol, 2006;32:4:227–248.

6. Janka A, Bielaszewska M, Dobrindt U, Greune L et al. Cytolethal distending toxin gene cluster in enterohemorrhagic Escherichia coli O157:H- and O157:H7: characterization and evolutionary considera­tions. Infect Immun, 2003;71:3634–3638.

7. Čurová K, Kmeťová M, Sabol M, Gombošová L, Lazúrová I, Siegfried L. Enterovirulent E. coli in inflammatory and noninflammatory bowel diseases. Folia microbiologica, 2009;54(1):81–86.

8. Shima A, Hinenoya A, Asakura M, Sugimoto N, Tsukamoto T et al. Molecular characterizations of cytolethal distending toxin produced by Providencia alcalifaciens strains isolated from patients with diarrhea. Infect. and Immun, 2012;80(4):1323–1332.

9. Abeck D, Freinkel AL, Korting HC, Szeimis RM, Ballard RC. Immunohistochemical investigations of genital ulcers caused by Haemophilus ducreyi. J STD AIDS, 1997;8:585–588.

10. Yue M, Yang F, Yang J, Bel W et al. Complete genome sequence of Haemophilus parasuis SH0165. J Bacteriol, 2009;191:1359–1360.

11. Henderson B, Wilson M, Shar L, Ward J. M. Actinobacillus actinomycetemcomitans. J Med Microbiol, 2002;51:1013–1020.

12. Ge Z, Schauer DB, Fox JG. In vivo virulence properties of bacterial cytolethal-distending toxin. Cell Microbiol, 2008;10:1599–1607.

13. Liyanage NP, Manthey KC, Dassanayake RP, Kuszynski CA et al. Helicobacter hepaticus cytolethal distening toxin causes cell ­death in intestinal epithelial cells via mitochondrial apoptotic pathway. Helicobacter, 2010;15:98–107.

14. Scott DA, Kaper JB. Cloning and sequencing of the genes encoding Escherichia coli cytolethal distending toxin. Infect Immun 1994;62(1):244–251.

15. Heywood W, Henderson B, Nair SP. Cytolethal distending toxin: creating a gap in the cell cycle. J Med Microbiol, 2005;54:207–216.

16. Lara-Tejero M, Galán JE. CdtA, CdtB, and CdtC form a tripartite complex that is required for cytolethal distending toxin activity. Infect Immun, 2001;69:4358–4365.

17. Yamada T, Komoto J, Saiki K, Konishi K et al. Variation of loop sequence alters stability of cytolethal distending toxin (CDT): crystal structure of CDT from Actinobacillus actinomycetemcomitans. Protein Sci, 2006;15:362–372.

18. Tóth I, Nougayréde JP, Dobrindt U, Ledger TN et al. Cytolethal distending toxin type I and type IV genes are framed with lambdoid prophage genes in extraintestinal pathogenic Escherichia coli. Infect Immun, 2009;77:492–500.

19. Johnson TJ, DebRoy C, Belton S, Williams ML et al. Pyrosequencing of the Vir plasmid of necrotoxigenic Escherichia coli. Vet Microbiol, 2010;144:100–109.

20. Doungudomdacha S, Volgina A, DiRienzo JM. Evidence that the cytolethal distending toxin locus was once part of a genomic island in the periodontal pathogen Aggregatibacter (Actinobacillus) actinomycetemcomitans strain Y4. J Med Microbiol, 2007;56:1519–1527.

21. Haghjoo E, Galán JE. Salmonella Typhi encodes a functional cytolethal distending toxin that is delivered into host cells by a bacterial-internalization pathway. Proc Nati Acad Sci USA, 2004;101:4614–4619.

22. Spanó S, Ugalde JE, Galán JE. Delivery of Salmonella Typhi exotoxin from a host intracellular compartment. Cell Host Microbe, 2008;3:30–38.

23. Gargi A, Reno M, Blanka SR. Bacterial toxin modulation of the eukaryotic cell cycle: are all cytolethal distending toxins created equally? Front Cell Inf Microbiol, 2012;2:124.

24. Dlakic M. Is CdtB a nuclease or a phosphatase? Science, 2001; 291:547.

25. Lara-Tejero M, Galan JE. Cytolethal distending toxin: limited damage as a strategy to modulate cellular functions. Trends Microbiol, 2002;10(3):147–152.

26. Pickett CL, Pesci EC, Cottle DL, Russell G, et al. Prevalence of cytolethal distending toxin production in Campylobacter jejuni and relatedness of Campylobacter sp. cdtB gene. Infect Immun, 1996;64(6):2070–2078.

27. Abuoun M, Manning G, Cawthraw SA, Ridley A, et al. Cytolethal distending toxin (CDT)-negative Campylobacter jejuni strains and anti-CDT neutralizing antibodies are induced during human infection but not during colonization in chickens. Infect Immun, 2005;73:3053–3062.

28. Lindmark B, Rompikuntal PK, Vaitkevicius K, Song T, et al. Outer membrane vesicle-mediated release of cytolethal distending toxin (CDT) from Campylobacter jejuni. BMC Microbiol, 2009;9:220.

29. Shenker BJ, Besack D, McKay T, Pankoski L, et al. Induction of cell cycle arrest in lymphocytes by Actinobacillus actinomycetemcomitans cytolethal distending toxin requires three subunits for maximum activity. J Immunol, 2005;174:2228–2234.

30. Guerra L, Cortes-Bratti X, Guidi R, Frisan T. The biology of the cytolethal distending toxins. Toxins, 2011;3(3):172–190.

31. Cortes-Bratti X, Chaves-Olarte E, Lagergård T, Thelestam M. Cellular internalization of cytolethal distending toxin from Haemophilus ducreyi. Infect Immun, 2000;68:6903–6911.

32. Guerra L, Nemec KN, Massey S, Tatulian SA, et al. A novel mode of translocation for cytolethal distending toxin. Biochim Biophys Acta, 2009;1793:489–495.

33. Lara-Tejero M, Galán JE. A bacterial toxin that controls cell cycle progression as a deoxyribonuclease I-like protein. Science, 2000;290:354–357.

34. Hassane DC, Lee RB, Mendenhall MD, Pickett CL. Cytolethal distending toxin demonstrates genotoxic aktivity in a yeast model. Infect Immun, 2001;69(9):5752–5759.

35. Frisan T, Cortes-Bratti X, Chaves-Olarte E, Stenerlöw B, et al. The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA. Cell Microbiol, 2003;5:695–707.

36. Fox JG, Ge Z, Whary MT, Erdman SE et al. Helicobacter hepaticus infection in mice: models for understanding lower bowel inflammation and cancer. Mucosal Immunol, 2011;4:22–30.

37. Ericsson AC, Myles M, Davis W, Ma L, et al. Noninvasive detection of inflammation-associated colon cancer in a mouse model. Neoplasia, 2010;12:1054–1065.

38. Hickey TE, McVeigh AL, Scott DA, Michielutti RE, et al. Campylobacter jejuni cytolethal distending toxin mediates release of interleukin-8 from intestinal epithelial cells. Infect Immun, 2000;68:6535–6541.

39. Whitehouse CA, Balbo PB, Pesci EC, Cottle DL, Mirabito PM, Pickett CL. Campylobacter jejuni cytolethal distending toxin causes a G2-phase cell cycle block. Infect Immun, 1998;66:1934–1940.

40. Albert MJ, Faruque SM, Faruque AS, Bettelheim KA, Neogi PK, et al. Controlled study of cytolethal distending toxin-producing Escherichia coli infections in Bangladeshi children. J Clin Microbiol, 1996;34(3):3717–3719.

41. Da Silva A, da Silva Leite D. Investigation of putative cdt gene in Escherichia coli isolates from pigs with diarrhea. Vet Microbiol, 2002;89:195–200.

42. Marques LRM, Tavechio AT, Abe CM, Gomes TAT. Search for cytolethal distending toxin production among fecal Escherichia coli isolates from brazilian children with diarrhea and without diarrhea. J Clin Microbiol, 2003;41(5):2206–2208.

43. Pérès SY, Marchès O, Daigle F, Nougayrède JP, et al. A new cytolethal distending toxin (CDT) from Escherichia coli producing CNF2 blocks HeLa cell division in G2/M phase. Mol Microbiol, 1997;24(5):1095–1107.

44. Okuda J, Fukumoto M, Takeda Y, Nishibuchi M. Examination of diarrheagenicity of cytolethal distending toxin: suckling mouse response to the products of the cdtABC genes of Shigella dysenteriae. Infect Immun, 1997;65:428–433.

45. Touati E. When bacteria become mutagenic and carcinogenic: lessons from H. pylori. Mutat Res, 2010;703:66–70.

46. Guigi R, Guerra L, Levi L, Stenerlöw B, et al. Chronic exposure to the cytolethal distending toxins of Gram-negative bacteria promotes genomic instability and altered DNA damage response. Cel Microbiol, 2013;15(1):98–113.

47. Trees DL, Morse SA. Chancroid and Haemophilus ducreyi: an ­update. Clin Microbiol Rev, 1995;8:357–375.

48. Wising C, Molne L, Jonsson JM, Ahlman K, et al. The cytolethal distending toxin of Haemophilus ducreyi aggravates dermal lessions in a rabbit model of chancroid. Microbes Infect, 2005;7(5–6):867–874.

49. Svensson LA, Henning P, Lagergård T. The cytolethal distending toxin of Haemophilus ducreyi inhibits endothelial cell proliferation. Infect Immun, 2002;70(5):2665–2669.

50. Xu T, Lundqvist A, Ahmed HJ, Eriksson K, et al. Interactions of Haemophilus ducreyi and purified cytolethal distending toxin with human monocyte-derived dendritic cells, macrophages and CD4+ T cells. Microb Infect, 2004;6(13):1171–1181.

51. Kováč J, Kováč D. Histopatológia a etiopatogenéza chronickej apikálnej parodontitídy – periapikálnych granulómov. Epidemiol Mikrobiol Imunol, 2011;60(2):77–86.

52. Henderson B, Ward JM, Ready D. Aggregatibacter (Actinobacillus) actinomycetemcomitans: a triple A* periodontopathogen? Periodontol, 2010;54:78–105.

53. Tan KS, Song KP, Ong G. Cytolethal distending toxin of Actinobacillus actinomycetemcomitans. Occurrence and association with periodontal disease. J Periodont Research, 2002;37:268–272.

54. Belibasakis G, Johansson A, Wang Y, Claesson R, et al. Inhibited proliferation of human periodontal ligament cells and gingival fibroblasts by Actinobacillus actinomycetemcomitans: involvement of the cytolethal distending toxin. Eur J Oral Sci, 2002;110(5):366–373.

55. Akifusa S, Poole S, Lewthwaite J, Henderson B, et al. 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, 2001;69:5925–5930.

56. Shenker BJ, McKay T, Datar S, Miller M, et al. Actinobacillus actinomycetemcomitans immunosuppressive protein is a member of the family of cytolethal distending toxins capable of causing a G2 arrest in human T cells. J Immunol, 1999;162:4773–4780.

Labels
Hygiene and epidemiology Medical virology Clinical microbiology

Article was published in

Epidemiology, Microbiology, Immunology

Issue 2

2014 Issue 2

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#