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Shiga toxin type 2 (Stx2), a potential agent of bioterrorism, has a short distribution and a long elimination half-life, and induces kidney and thymus lesions in rats

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Abstract

Shiga toxin type 2, a major virulence factor produced by the Shiga toxin–producing Escherichia coli, is a potential toxin agent of bioterrorism. In this study, iodine-125 (125I) was used as an indicator to describe the in vivo Stx2 biodistribution profile. The rats were injected intravenously (i.v.) with 125I-Stx2 at three doses of 5.1–127.5 μg/kg body weight. Stx2 had a short distribution half-life (t 1/2α, less than 6 min) and a long elimination half-life in rat. The toxicokinetics of Stx2 in rats was dose dependent and nonlinear. Stx2 concentrations in various tissues were detected at 5-min, 0.5-h, and 72-h postinjection. High radioactivity was found in the lungs, kidneys, nasal turbinates, and sometimes in the eyes, which has never been reported in previous studies. In a preliminary assessment, lesions were found in the kidney and thymus.

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References

  • Boyd B, Tyrrell G, Maloney M et al (1993) Alteration of the glycolipid binding specificity of the pig edema toxin from globotetraosyl to globotriaosyl ceramide alters in vivo tissue targeting and results in a VT1-like disease in pigs. J Exp Med 177:1745–1753

    Article  PubMed  CAS  Google Scholar 

  • Burdet J, Zotta E, Franchi AM, Ibarra C (2009) Intraperitoneal administration of Shiga toxin type 2 in rats in the late stage of pregnancy produces premature delivery of dead fetuses. Placenta 30:491–496

    Article  PubMed  CAS  Google Scholar 

  • Feng J, Mehta VB, El-Assal ON, Wu D, Besner GE (2006) Tissue distribution and plasma clearance of heparin-binding EGF-like growth factor (HB-EGF) in adult and newborn rats. Peptides 27:1589–1596

    Article  PubMed  CAS  Google Scholar 

  • Kaye SA, Louise CB, Boyd B, Lingwood CA, Obrig TG (1993) Shiga toxin-associated hemolytic uremic syndrome: interleukin-1 beta enhancement of Shiga toxin cytotoxicity toward human vascular endothelial cells in vitro. Infect Immun 61:3886–3891

    PubMed  CAS  Google Scholar 

  • Keepers TR, Psotka MA, Gross LK, Obrig TG (2006) A murine model of HUS: shiga toxin with lipopolysaccharide mimics the renal damage and physiologic response of human disease. J Am Soc Nephrol 17:3404–3414

    Article  PubMed  CAS  Google Scholar 

  • Khine AA, Lingwood CA (1994) Capping and receptor-mediated endocytosis of cell-bound verotoxin (Shiga-like toxin). 1: chemical identification of an amino acid in the B subunit necessary for efficient receptor glycolipid binding and cellular internalization. J Cell Physiol 161:319–332

    Article  PubMed  CAS  Google Scholar 

  • Kleanthous H, Smith HR, Scotland SM, Gross RJ, Rowe B, Taylor CM, Milford DV (1990) Haemolytic uraemic syndromes in the British Isles, 1985–1988: association with verocytotoxin producing Escherichia coli. Part 2: microbiological aspects. Arch Dis Child 65:722–727

    Article  PubMed  CAS  Google Scholar 

  • Louise CB, Obrig TG (1995) Specific interaction of Escherichia coli O157:H7-derived Shiga-like toxin II with human renal endothelial cells. J Infect Dis 172(5):1397–1401

    Article  PubMed  CAS  Google Scholar 

  • Milford DV, Taylor CM, Guttridge B, Hall SM, Rowe B, Kleanthous H (1990) Haemolytic uraemic syndromes in the British Isles 1985–1988: association with verocytotoxin producing Escherichia coli. Part 1: clinical and epidemiological aspects. Arch Dis Child 65:716–721

    Article  PubMed  CAS  Google Scholar 

  • Ngeleka M, Pritchard J, Appleyard G, Middleton DM, Fairbrother JM (2003) Isolation and association of Escherichia coli AIDA-I/STb, rather than EAST1 pathotype, with diarrhea in piglets and antibiotic sensitivity of isolates. J Vet Diagn Invest 15:242–252

    Article  PubMed  Google Scholar 

  • Paton JC, Paton AW (1998) Pathogenesis and diagnosis of Shiga toxin-producing Escherichia coli infections. Clin Microbiol Rev 11:450–479

    PubMed  CAS  Google Scholar 

  • Pellizzari A, Pang H, Lingwood CA (1992) Binding of verocytotoxin 1 to its receptor is influenced by differences in receptor fatty acid content. Biochemistry 31:1363–1370

    Article  PubMed  CAS  Google Scholar 

  • Psotka MA, Obata F, Kolling GL, Gross LK, Saleem MA, Satchell SC, Mathieson PW, Obrig TG (2009) Shiga toxin 2 targets the murine renal collecting duct epithelium. Infect Immun 77:959–969

    Article  PubMed  CAS  Google Scholar 

  • Richardson SE, Rotman TA, Jay V, Smith CR, Becker LE, Petric M, Olivieri NF, Karmali MA (1992) Experimental verocytotoxemia in rabbits. Infect Immun 60:4154–4167

    PubMed  CAS  Google Scholar 

  • Rutjes NW, Binnington BA, Smith CR, Maloney MD, Lingwood CA (2002) Differential tissue targeting and pathogenesis of verotoxins 1 and 2 in the mouse animal model. Kidney Int 62:832–845

    Article  PubMed  CAS  Google Scholar 

  • Sandvig K, Olsnes S, Brown JE, Petersen OW, van Deurs B (1989) Endocytosis from coated pits of Shiga toxin: a glycolipid-binding protein from Shigella dysenteriae. J Cell Biol 108:1331–1343

    Article  PubMed  CAS  Google Scholar 

  • Sandvig K, Garred O, Prydz K, Kozlov JV, Hansen SH, van Deurs B (1992) Retrograde transport of endocytosed Shiga toxin to the endoplasmic reticulum. Nature 358:510–512

    Article  PubMed  CAS  Google Scholar 

  • Scotland SM, Willshaw GA, Smith HR, Rowe B (1987) Properties of strains of Escherichia coli belonging to serogroup O157 with special reference to production of Vero cytotoxins VT1 and VT2. Epidemiol Infect 99:613–624

    Article  PubMed  CAS  Google Scholar 

  • Siegler RL, Obrig TG, Pysher TJ, Tesh VL, Denkers ND, Taylor FB (2003) Response to Shiga toxin 1 and 2 in a baboon model of hemolytic uremic syndrome. Pediatr Nephrol (Berlin, Germany) 18:92–96

    Google Scholar 

  • Stevens CD, Stewart PH et al (1949) The distribution of radioactive iodine in rats with and without walker tumor 256 after injection of radioactive sodium iodide. Cancer Res 9:488–497

    PubMed  CAS  Google Scholar 

  • Sugatani J, Komiyama N, Mochizuki T et al (2002) Urinary concentrating defect in rats given Shiga toxin: elevation in urinary AQP2 level associated with polyuria. Life Sci 71:171–189

    Article  PubMed  CAS  Google Scholar 

  • Tapper D, Tarr P, Avner E, Brandt J, Waldhausen J (1995) Lessons learned in the management of hemolytic uremic syndrome in children. J Pediatr Surg 30:158–163

    Article  PubMed  CAS  Google Scholar 

  • Tarr PI, Gordon CA, Chandler WL (2005) Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 365:1073–1086

    PubMed  CAS  Google Scholar 

  • Tesh VL, Burris JA, Owens JW, Gordon VM, Wadolkowski EA, O’Brien AD, Samuel JE (1993) Comparison of the relative toxicities of Shiga-like toxins type I and type II for mice. Infect Immun 61:3392–3402

    PubMed  CAS  Google Scholar 

  • Valles PG, Pesle S, Piovano L, Azuma K (2005) Postdiarrheal Shiga toxin-mediated hemolytic uremic syndrome similar to septic shock. Medicina 65:395–401

    PubMed  Google Scholar 

  • Watanabe PG, Young JD, Gehring PJ (1977) The importance of non-linear (dose-dependent) pharmacokinetics in hazard assessment. J Environ Pathol Toxicol 1:147–159

    PubMed  CAS  Google Scholar 

  • Wei T, Kun C, Xiang G, Le X, Rongchang CH, Jing Sh Xiaojun H, Qin W, Wang H (2009) Improved production of holotoxin Stx2 with biological activities by using a single-promoter vector and an auto-induction expression system. Protein Expr Purif 67:169–174

    Article  Google Scholar 

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Acknowledgments

This work is supported by National Natural Science Foundation of China (No.30901278 and No.81072677), and in part by the grant from National Grand Program of China (2008ZX10004-015).

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Correspondence to Jian-Chun Li or Hui Wang.

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Yue-Nan Liu and Sheng-han Wang have contributed equally to this work.

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Liu, YN., Wang, Sh., Li, T. et al. Shiga toxin type 2 (Stx2), a potential agent of bioterrorism, has a short distribution and a long elimination half-life, and induces kidney and thymus lesions in rats. Arch Toxicol 85, 1133–1140 (2011). https://doi.org/10.1007/s00204-010-0639-0

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  • DOI: https://doi.org/10.1007/s00204-010-0639-0

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