1887

Abstract

serotype Typhimurium ( Typhimurium) definitive phage type (DT) 104 has become a widespread cause of human and other animal infections worldwide. The severity of clinical illness in Typhimurium DT104 outbreaks suggests that this strain possesses enhanced virulence. ArtA and ArtB – encoded by a prophage in Typhimurium DT104 – are homologues of components of pertussis toxin (PTX), including its ADP-ribosyltransferase subunit. Here, we show that exposing DT104 to mitomycin C, a DNA-damaging agent, induced production of prophage-encoded ArtA/ArtB. Pertussis-sensitive G proteins were labelled in the presence of [P]NAD and ArtA, and the label was released by HgCl, which is known to cleave cysteine-ADP-ribose bonds. ADP-dependent modification of G proteins was markedly reduced in -synthesized ArtA and ArtA, in which alanine was substituted for the conserved arginine at position 6 (necessary for NAD binding) and the predicted catalytic glutamate at position 115, respectively. A cellular ADP-ribosylation assay and two-dimensional electrophoresis showed that ArtA- and PTX-induced ADP-ribosylation in Chinese hamster ovary (CHO) cells occur with the same type of G proteins. Furthermore, exposing CHO cells to the ArtA/ArtB-containing culture supernatant of DT104 resulted in a clustered growth pattern, as is observed in PTX-exposed CHO cells. Hydrogen peroxide, an oxidative stressor, also induced ArtA/ArtB production, suggesting that these agents induce synthesis of ArtA/ArtB. These results, taken together, suggest that ArtA/ArtB is an active toxin similar to PTX.

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2009-11-01
2020-10-26
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References

  1. Aktories K., Weller U., Chhatwal G. S.. 1987; Clostridium botulinum type C produces a novel ADP-ribosyltransferase distinct from botulinum C2 toxin. FEBS Lett212:109–113
    [Google Scholar]
  2. Allen C. A., Fedorka-Cray P. J., Vazquez-Torres A., Suyemoto M., Altier C., Ryder L. R., Fang F. C., Libby S. J.. 2001; In vitro and in vivo assessment of Salmonella enterica serovar Typhimurium DT104 virulence. Infect Immun69:4673–4677
    [Google Scholar]
  3. Briggs C. E., Fratamico P. M.. 1999; Molecular characterization of an antibiotic resistance gene cluster of Salmonella typhimurium DT104. Antimicrob Agents Chemother43:846–849
    [Google Scholar]
  4. Burnette W. N.. 1994; AB5 ADP-ribosylating toxins: comparative anatomy and physiology. Structure2:151–158
    [Google Scholar]
  5. Carlson S. A., Meyerholz D. K., Stabel T. J., Jones B. D.. 2001; Secretion of a putative cytotoxin in multiple antibiotic resistant Salmonella enterica serotype Typhimurium phagetype DT104. Microb Pathog31:201–204
    [Google Scholar]
  6. Carroll S. F., Collier R. J.. 1984; NAD binding site of diphtheria toxin: identification of a residue within the nicotinamide subsite by photochemical modification with NAD. Proc Natl Acad Sci U S A81:3307–3311
    [Google Scholar]
  7. Collier R. J.. 2001; Understanding the mode of action of diphtheria toxin: a perspective on progress during the 20th century. Toxicon39:1793–1803
    [Google Scholar]
  8. Domenighini M., Rappuoli R.. 1996; Three conserved consensus sequences identify the NAD-binding site of ADP-ribosylating enzymes, expressed by eukaryotes, bacteria and T-even bacteriophages. Mol Microbiol21:667–674
    [Google Scholar]
  9. Figueroa-Bossi N., Bossi L.. 1999; Inducible prophages contribute to Salmonella virulence in mice. Mol Microbiol33:167–176
    [Google Scholar]
  10. Finkelstein R. A., Atthasampunna P., Chulasamaya M., Charunmethee P.. 1966; Pathogenesis of experimental cholera: biologic ativities of purified procholeragen A. J Immunol96:440–449
    [Google Scholar]
  11. Glynn M. K., Bopp C., Dewitt W., Dabney P., Mokhtar M., Angulo F. J.. 1998; Emergence of multidrug-resistant Salmonella enterica serotype typhimurium DT104 infections in the United States. N Engl J Med338:1333–1338
    [Google Scholar]
  12. Guerrant R. L., Brunton L. L., Schnaitman T. C., Rebhun L. I., Gilman A. G.. 1974; Cyclic adenosine monophosphate and alteration of Chinese hamster ovary cell morphology: a rapid, sensitive in vitro assay for the enterotoxins of Vibrio cholerae and Escherichia coli. Infect Immun10:320–327
    [Google Scholar]
  13. Han S., Craig J. A., Putnam C. D., Carozzi N. B., Tainer J. A.. 1999; Evolution and mechanism from structures of an ADP-ribosylating toxin and NAD complex. Nat Struct Biol6:932–936
    [Google Scholar]
  14. Hewlett E. L., Sauer K. T., Myers G. A., Cowell J. L., Guerrant R. L.. 1983; Induction of a novel morphological response in Chinese hamster ovary cells by pertussis toxin. Infect Immun40:1198–1203
    [Google Scholar]
  15. Ho S. N., Hunt H. D., Horton R. M., Pullen J. K., Pease L. R.. 1989; Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene77:51–59
    [Google Scholar]
  16. Imlay J. A., Linn S.. 1987; Mutagenesis and stress responses induced in Escherichia coli by hydrogen peroxide. J Bacteriol169:2967–2976
    [Google Scholar]
  17. Kannan T. R., Baseman J. B.. 2006; ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents unique virulence determinant among bacterial pathogens. Proc Natl Acad Sci U S A103:6724–6729
    [Google Scholar]
  18. Katada T., Ui M.. 1982; Direct modification of the membrane adenylate cyclase system by islet-activating protein due to ADP-ribosylation of a membrane protein. Proc Natl Acad Sci U S A79:3129–3133
    [Google Scholar]
  19. Krueger K. M., Barbieri J. T.. 1995; The family of bacterial ADP-ribosylating exotoxins. Clin Microbiol Rev8:34–47
    [Google Scholar]
  20. Laemmli U. K.. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227:680–685
    [Google Scholar]
  21. Lesnick M. L., Reiner N. E., Fierer J., Guiney D. G.. 2001; The Salmonella spvB virulence gene encodes an enzyme that ADP-ribosylates actin and destabilizes the cytoskeleton of eukaryotic cells. Mol Microbiol39:1464–1470
    [Google Scholar]
  22. Locht C.. 1999; Molecular aspects of Bordetella pertussis pathogenesis. Int Microbiol2:137–144
    [Google Scholar]
  23. Maehama T., Nishina H., Hoshino S., Kanaho Y., Katada T.. 1995; NAD+-dependent ADP-ribosylation of T lympocyte alloantigen RT6.1 reversibly proceeding in intact rat lymphocytes. J Biol Chem270:22747–22751
    [Google Scholar]
  24. Mekalanos J. J., Collier R. J., Romig W. R.. 1979; Enzymic activity of cholera toxin. I. New method of assay and the mechanism of ADP-ribosyl transfer. J Biol Chem254:5849–5854
    [Google Scholar]
  25. Merritt E. A., Hol W. G.. 1995; AB5 toxins. Curr Opin Struct Biol5:165–171
    [Google Scholar]
  26. Moss J., Stanley S. J., Burns D. L., Hsia J. A., Yost D. A., Myers G. A., Hewlett E. L.. 1983; Activation by thiol of the latent NAD glycohydrolase and ADP-ribosyltransferase activities of Bordetella pertussis toxin (islet-activating protein. J Biol Chem258:11879–11882
    [Google Scholar]
  27. Pallen M. J., Lam A. C., Loman N. J., McBride A.. 2001; An abundance of bacterial ADP-ribosyltransferases – implications for the origin of exotoxins and their human homologues. Trends Microbiol9:302–307
    [Google Scholar]
  28. Saitoh M., Tanaka K., Nishimori K., Makino S., Kanno T., Ishihara R., Hatama S., Kitano R., Kishima M.. other authors 2005; The artAB genes encode a putative ADP-ribosyltransferase toxin homologue associated with Salmonella enterica serovar Typhimurium DT104. Microbiology151:3089–3096
    [Google Scholar]
  29. Sameshima T., Akiba M., Izumiya H., Terajima J., Tamura K., Watanabe H., Nakazawa M.. 2000; Salmonella typhimurium DT104 from livestock in Japan. Jpn J Infect Dis53:15–16
    [Google Scholar]
  30. Sandvang D., Aarestrup F. M., Jensen L. B.. 1998; Characterisation of integrons and antibiotic resistance genes in Danish multiresistant Salmonella enterica Typhimurium DT104. FEMS Microbiol Lett160:37–41
    [Google Scholar]
  31. Schering B., Barmann M., Chhatwal G. S., Geipel U., Aktories K.. 1988; ADP-ribosylation of skeletal muscle and non-muscle actin by Clostridium perfringens iota toxin. Eur J Biochem171:225–229
    [Google Scholar]
  32. Spano S., Ugalde J. E., Galan J. E.. 2008; Delivery of a Salmonella Typhi exotoxin from a host intracellular compartment. Cell Host Microbe3:30–38
    [Google Scholar]
  33. Threlfall E. J., Frost J. A., Ward L. R., Rowe B.. 1994; Epidemic in cattle and humans of Salmonella typhimurium DT 104 with chromosomally integrated multiple drug resistance. Vet Rec134:577
    [Google Scholar]
  34. Villar R. G., Macek M. D., Simons S., Hayes P. S., Goldoft M. J., Lewis J. H., Rowan L. L., Hursh D., Patnode M., Mead P. S.. 1999; Investigation of multidrug-resistant Salmonella serotype typhimurium DT104 infections linked to raw-milk cheese in Washington State. JAMA281:1811–1816
    [Google Scholar]
  35. Wagner P. L., Waldor M. K.. 2002; Bacteriophage control of bacterial virulence. Infect Immun70:3985–3993
    [Google Scholar]
  36. Wagner P. L., Acheson D. W., Waldor M. K.. 2001; Human neutrophils and their products induce Shiga toxin production by enterohemorrhagic Escherichia coli. Infect Immun69:1934–1937
    [Google Scholar]
  37. Xu Y., Barbieri J. T.. 1995; Pertussis toxin-mediated ADP-ribosylation of target proteins in Chinese hamster ovary cells involves a vesicle trafficking mechanism. Infect Immun63:825–832
    [Google Scholar]
  38. Xu Y., Barbieri J. T.. 1996; Pertussis toxin-catalyzed ADP-ribosylation of Gi-2 and Gi-3 in CHO cells is modulated by inhibitors of intracellular trafficking. Infect Immun64:593–599
    [Google Scholar]
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