Pathogenesis of Shiga-Toxin Producing Escherichia coli

  • Angela Melton-Celsa
  • Krystle Mohawk
  • Louise Teel
  • Alison O’BrienEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 357)


Shiga toxin (Stx)-producing Escherichia coli (STEC) are food-borne pathogens that cause hemorrhagic colitis and a serious sequela, the hemolytic uremic syndrome (HUS). The largest outbreaks of STEC are due to a single E. coli serotype, O157:H7, although non-O157 serotypes also cause the same diseases. Two immunologically distinct Stxs are found in E. coli, Stx1 and Stx2. The Stxs are AB5 toxins that halt protein synthesis in the host cell, a process that may lead to an apoptotic cell death. Stx-mediated damage to renal glomerular endothelial cells is hypothesized as the precipitating event for HUS. A subset of STEC referred to as the enterohemorrhagic E. coli has the capacity to intimately attach to and efface intestinal epithelial cells, a pathology called the A/E lesion. The A/E lesion is mediated by the adhesin intimin, its bacterially encoded receptor, Tir, and effectors secreted through a type III secretion system. The proteins needed for the A/E lesion are encoded within a large pathogenicity island called the locus of enterocyte effacement or LEE. There are several animal models for STEC infection, but no one model fully represents the spectrum of STEC illness. Currently there is no cure for STEC infection, and therapies are based mainly on alleviating symptoms. However, chimeric or humanized monoclonal antibodies have been developed that neutralize the Stxs, and those therapies may be able to prevent the development of HUS in an STEC-infected patient.


Hemolytic Uremic Syndrome T3SS Effector Hemolytic Uremic Syndrome Patient Lambdoid Phage Gnotobiotic Piglet 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We wish to acknowledge that much of our understanding of STEC has come about through research funded by the NIH grant AI20148.


  1. Abu-Ali GS, Ouellette LM, Henderson ST, Lacher DW, Riordan JT, Whittam TS, Manning SD (2010) Increased adherence and expression of virulence genes in a lineage of Escherichia coli O157:H7 commonly associated with human infections. PLoS.ONE 5:e10167. doi: 10.1371/journal.pone.0010167 PubMedCrossRefGoogle Scholar
  2. Abu-Median AB, van Diemen PM, Dziva F, Vlisidou I, Wallis TS, Stevens MP (2006) Functional analysis of lymphostatin homologues in enterohaemorrhagic Escherichia coli. FEMS Microbiol Lett 258:43–49. doi: 10.1111/j.1574-6968.2006.00198.x PubMedCrossRefGoogle Scholar
  3. Acheson DW, Moore R, De Breucker S, Lincicome L, Jacewicz M, Skutelsky E, Keusch GT (1996) Translocation of Shiga toxin across polarized intestinal cells in tissue culture. Infect Immun 64:3294–3300PubMedGoogle Scholar
  4. Ahmed A, Li J, Shiloach Y, Robbins JB, Szu SC (2006) Safety and immunogenicity of Escherichia coli O157 O-specific polysaccharide conjugate vaccine in 2–5-year-old children. J Infect Dis 193:515–521PubMedCrossRefGoogle Scholar
  5. Ake JA, Jelacic S, Ciol MA, Watkins SL, Murray KF, Christie DL, Klein EJ, Tarr PI (2005) Relative nephroprotection during Escherichia coli O157:H7 infections: association with intravenous volume expansion. Pediatrics 115:e673–e680. doi: 10.1542/peds.2004-2236 PubMedCrossRefGoogle Scholar
  6. Andreoli SP, Trachtman H, Acheson DW, Siegler RL, Obrig TG (2002) Hemolytic uremic syndrome: epidemiology, pathophysiology, and therapy. Pediatr Nephrol 17:293–298PubMedCrossRefGoogle Scholar
  7. Asadulghani M, Ogura Y, Ooka T, Itoh T, Sawaguchi A, Iguchi A, Nakayama K, Hayashi T (2009) The defective prophage pool of Escherichia coli O157: prophage–prophage interactions potentiate horizontal transfer of virulence determinants. PLoS Pathog 5:e1000408. doi: 10.1371/journal.ppat.1000408 PubMedCrossRefGoogle Scholar
  8. Ashkenazi S, Larocco M, Murray BE, Cleary TG (1992) The adherence of verocytotoxin-producing Escherichia coli to rabbit intestinal cells. J Med Microbiol 37:304–309PubMedCrossRefGoogle Scholar
  9. Baines D, Lee B, McAllister T (2008) Heterogeneity in enterohemorrhagic Escherichia coli O157:H7 fecal shedding in cattle is related to Escherichia coli O157:H7 colonization of the small and large intestine. Can J Microbiol 54:984–995. doi: 10.1139/w08-090 PubMedCrossRefGoogle Scholar
  10. Banatvala N, Griffin PM, Greene KD, Barrett TJ, Bibb WF, Green JH, Wells JG (2001) The United States national prospective hemolytic uremic syndrome study: microbiologic, serologic, clinical, and epidemiologic findings. J Infect Dis 183:1063–1070PubMedCrossRefGoogle Scholar
  11. Beery JT, Doyle MP, Schoeni JL (1985) Colonization of chicken cecae by Escherichia coli associated with hemorrhagic colitis. Appl Environ Microbiol 49:310–315PubMedGoogle Scholar
  12. Berry ED, Wells JE (2010) Escherichia coli O157:H7 Recent Advances in Research on Occurrence, Transmission, and Control in Cattle and the Production Environment. Adv Food Nutr Res 60:67–117. doi: 10.1016/S1043-4526(10)60004-6 PubMedCrossRefGoogle Scholar
  13. Beutin L, Montenegro MA, Orskov I, Orskov F, Prada J, Zimmermann S, Stephan R (1989) Close association of verotoxin (Shiga-like toxin) production with enterohemolysin production in strains of Escherichia coli. J Clin Microbiol 27:2559–2564PubMedGoogle Scholar
  14. Bielaszewska M, Friedrich AW, Aldick T, Schurk-Bulgrin R, Karch H (2006) Shiga toxin activatable by intestinal mucus in Escherichia coli isolated from humans: predictor for a severe clinical outcome. Clin Infect Dis 43:1160–1167PubMedCrossRefGoogle Scholar
  15. Bielaszewska M, Stoewe F, Fruth A, Zhang W, Prager R, Brockmeyer J, Mellmann A, Karch H, Friedrich AW (2009) Shiga toxin, cytolethal distending toxin, and hemolysin repertoires in clinical Escherichia coli O91 isolates. J Clin Microbiol 47:2061–2066. doi: 10.1128/JCM.00201-09 PubMedCrossRefGoogle Scholar
  16. Bitzan M, Moebius E, Ludwig K, Müller-Wiefel DE, Heesemann J, Karch H (1991) High incidence of serum antibodies to Escherichia coli O157 lipopolysaccharide in children with hemolytic-uremic syndrome. J Pediatr 119:380–385PubMedCrossRefGoogle Scholar
  17. Bitzan M, Poole R, Mehran M, Sicard E, Brockus C, Thuning-Roberson C, Rivière M (2009) Safety and pharmacokinetics of chimeric anti-Shiga toxin 1 and anti-Shiga toxin 2 monoclonal antibodies in healthy volunteers. Antimicrob Agents Chemother 53:3081–3087. doi: 10.1128/AAC.01661-08 PubMedCrossRefGoogle Scholar
  18. Brando RJ, Miliwebsky E, Bentancor L, Deza N, Baschkier A, Ramos MV, Fernández GC, Meiss R, Rivas M, Palermo MS (2008) Renal damage and death in weaned mice after oral infection with Shiga toxin 2-producing Escherichia coli strains. Clin Exp Immunol 153:297–306PubMedCrossRefGoogle Scholar
  19. Brigotti M, Tazzari PL, Ravanelli E, Carnicelli D, Barbieri S, Rocchi L, Arfilli V, Scavia G, Ricci F, Bontadini A, Alfieri RR, Petronini PG, Pecoraro C, Tozzi AE, Caprioli A (2010) Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration. J.Leukoc Biol 88:201–210. doi: 10.1189/jlb.0709475 PubMedCrossRefGoogle Scholar
  20. Brooks JT, Sowers EG, Wells JG, Greene KD, Griffin PM, Hoekstra RM, Strockbine NA (2005) Non-O157 Shiga toxin-producing Escherichia coli infections in the United States, 1983–2002. J Infect Dis 192:1422–1429PubMedCrossRefGoogle Scholar
  21. Brown CA, Harmon BG, Zhao T, Doyle MP (1997) Experimental Escherichia coli O157:H7 carriage in calves. Appl Environ Microbiol 63:27–32PubMedGoogle Scholar
  22. Brunder W, Schmidt H, Karch H (1997) EspP, a novel extracellular serine protease of enterohaemorrhagic Escherichia coli O157:H7 cleaves human coagulation factor V. Mol Microbiol 24:767–778PubMedCrossRefGoogle Scholar
  23. Brunder W, Schmidt H, Frosch M, Karch H (1999) The large plasmids of Shiga-toxin-producing Escherichia coli (STEC) are highly variable genetic elements. Microbiology 145(Pt 5):1005–1014PubMedCrossRefGoogle Scholar
  24. Calderwood SB, Mekalanos JJ (1987) Iron regulation of Shiga-like toxin expression in Escherichia coli is mediated by the fur locus. J Bacteriol 169:4759–4764PubMedGoogle Scholar
  25. Caletti MG, Balestracci A, Roy AH (2010) Levels of urinary transforming growth factor β1 in children with D + hemolytic uremic syndrome. Pediatr Nephrol 25:1177–1180. doi: 10.1007/s00467-009-1434-0 PubMedCrossRefGoogle Scholar
  26. Campellone KG, Leong JM (2003) Tails of two Tirs: actin pedestal formation by enteropathogenic E. coli and enterohemorrhagic E. coli O157:H7. Curr Opin Microbiol 6:82–90PubMedCrossRefGoogle Scholar
  27. Centers for Disease Control, Prevention (1995) Outbreak of acute gastroenteritis attributable to Escherichia coli serotype O104:H21––Helena, Montana, 1994 MMWR 44:501–503Google Scholar
  28. Clark WF, Sontrop JM, Macnab JJ, Salvadori M, Moist L, Suri R, Garg AX (2010) Long term risk for hypertension, renal impairment, and cardiovascular disease after gastroenteritis from drinking water contaminated with Escherichia coli O157:H7: a prospective cohort study. BMJ 341:c6020PubMedCrossRefGoogle Scholar
  29. Conlan JW, Perry MB (1998) Susceptibility of three strains of conventional adult mice to intestinal colonization by an isolate of Escherichia coli O157:H7. Can J Microbiol 44:800–805PubMedGoogle Scholar
  30. Conradi H (1903) Uber iosliche, durch asptische autolyse erhaltene Giftstoffe vonRuhr- und typhus-bazillen. Dtsch Med Wochenschr 29:26–28CrossRefGoogle Scholar
  31. Cornick NA, Matise I, Samuel JE, Bosworth BT, Moon HW (2000) Shiga toxin-producing Escherichia coli infection: temporal and quantitative relationships among colonization, toxin production, and systemic disease. J Infect Dis 181:242–251. doi: 10.1086/315172 PubMedCrossRefGoogle Scholar
  32. Cornick NA, Booher SL, Moon HW (2002) Intimin facilitates colonization by Escherichia coli O157:H7 in adult ruminants. Infect Immun 70:2704–2707PubMedCrossRefGoogle Scholar
  33. Cray WC Jr, Moon HW (1995) Experimental infection of calves and adult cattle with Escherichia coli O157:H7. Appl Environ Microbiol 61:1586–1590PubMedGoogle Scholar
  34. Currie CG, McCallum K, Poxton IR (2001) Mucosal and systemic antibody responses to the lipopolysaccharide of Escherichia coli O157 in health and disease. J Med Microbiol 50:345–354PubMedGoogle Scholar
  35. CDC (2005) Outbreaks of Escherichia coli O157:H7 associated with petting zoos—North Carolina, Florida, and Arizona, 2004 and 2005. MMW 54:1277-1280Google Scholar
  36. Deacon V, Dziva F, van Diemen PM, Frankel G, Stevens MP (2010) Efa-1/LifA mediates intestinal colonization of calves by enterohaemorrhagic Escherichia coli O26 : H-in a manner independent of glycosyltransferase and cysteine protease motifs or effects on type III secretion. Microbiology 156:2527–2536. doi: 10.1099/mic.0.039685-0 PubMedCrossRefGoogle Scholar
  37. Dean-Nystrom EA, Bosworth BT, Cray WC Jr, Moon HW (1997) Pathogenicity of Escherichia coli O157:H7 in the intestines of neonatal calves. Infect Immun 65:1842–1848PubMedGoogle Scholar
  38. Dean-Nystrom EA, Bosworth BT, Moon HW, O’Brien AD (1998) Escherichia coli O157:H7 requires intimin for enteropathogenicity in calves. Infect Immun 66:4560–4563PubMedGoogle Scholar
  39. Dean-Nystrom EA, Bosworth BT, Moon HW (1999) Pathogenesis of Escherichia coli O157:H7 in weaned calves. Adv Exp Med Biol 473:173–177PubMedCrossRefGoogle Scholar
  40. Dong T, Schellhorn HE (2009) Global effect of RpoS on gene expression in pathogenic Escherichia coli O157:H7 strain EDL933 BMC. Genomics 10:349. doi: 10.1186/1471-2164-10-349 PubMedGoogle Scholar
  41. Dowling TC, Chavaillaz PA, Young DG, Melton-Celsa A, O’Brien A, Thuning-Roberson C, Edelman R, Tacket CO (2005) Phase 1 safety and pharmacokinetic study of chimeric murine-human monoclonal antibody cαStx2 administered intravenously to healthy adult volunteers. Antimicrob Agents Chemother 49:1808–1812PubMedCrossRefGoogle Scholar
  42. Dziva F, Mahajan A, Cameron P, Currie C, McKendrick IJ, Wallis TS, Smith DG, Stevens MP (2007) EspP, a Type V-secreted serine protease of enterohaemorrhagic Escherichia coli O157:H7, influences intestinal colonization of calves and adherence to bovine primary intestinal epithelial cells FEMS. Microbiol Lett 271:258–264. doi: 10.1111/j.1574-6968.2007.00724.x CrossRefGoogle Scholar
  43. Edwards AC, Melton-Celsa AR, Arbuthnott K, Stinson JR, Schmitt CK, Wong HC, O’Brien AD (1998) Vero cell neutralization and mouse protective efficacy of humanized monoclonal antibodies against Escherichia coli toxins Stx1 and Stx2. In: Kaper JB, O’Brien AD (eds) Escherichia coli O157:H7 and other Shiga toxin-producing E coli strains. ASM Press, Washington, DC, pp 388–392Google Scholar
  44. Endo Y, Mitsui K, Motizuki M, Tsurugi K (1987) The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28 S ribosomal RNA caused by the toxins. J Biol Chem 262:5908–5912Google Scholar
  45. Farmer JJ III, Potter ME, Riley LW, Barrett TJ, Blake PA, Bopp CA, Cohen ML, Kaufmann A, Morris GK, Remis RS, Thomason BM, Wells JG (1983) Animal models to study Escherichia coli O157:H7 isolated from patients with haemorrhagic colitis. Lancet 1:702–703PubMedCrossRefGoogle Scholar
  46. Fegan N, Desmarchelier P (2002) Comparison between human and animal isolates of Shiga toxin-producing Escherichia coli O157 from Australia. Epidemiol Infect 128:357–362PubMedCrossRefGoogle Scholar
  47. Feng P, Lampel KA, Karch H, Whittam TS (1998) Genotypic and phenotypic changes in the emergence of Escherichia coli O157:H7. J Infect Dis 177:1750–1753PubMedCrossRefGoogle Scholar
  48. Fenwick BW, Cowan LA (1998) Canine model of the hemolytic uremic syndrome. In: Kaper JB, O’Brien AD (eds) Escherichia coli O157:H7 and other Shiga toxin-producing E coli. ASM Press, Washington, DC, pp 268–277Google Scholar
  49. Ferens WA, Hovde CJ (2010) Escherichia coli O157:H7: animal reservoir and sources of human infection. Foodborne Pathog Dis. doi: 10.1089/fpd.2010.0673 PubMedGoogle Scholar
  50. Fontaine A, Arondel J, Sansonetti PJ (1988) Role of Shiga toxin in the pathogenesis of bacillary dysentery, studied by using a Tox-mutant of Shigella dysenteriae 1. Infect Immun 56:3099–3109PubMedGoogle Scholar
  51. Foster JW (2004) Escherichia coli acid resistance: tales of an amateur acidophile. Nat Rev Microbiol 2:898–907. doi: 10.1038/nrmicro1021 PubMedCrossRefGoogle Scholar
  52. Francis DH, Collins JE, Duimstra JR (1986) Infection of gnotobiotic pigs with an Escherichia coli O157:H7 strain associated with an outbreak of hemorrhagic colitis. Infect Immun 51:953–956PubMedGoogle Scholar
  53. Fratamico PM, Bhaduri S, Buchanan RL (1993) Studies on Escherichia coli serotype O157:H7 strains containing a 60-MDa plasmid and on 60-MDa plasmid-cured derivatives. J Med Microbiol 39:371–381PubMedCrossRefGoogle Scholar
  54. Fratamico PM, Yan X, Caprioli A, Esposito G, Needleman DS, Pepe T, Tozzoli R, Cortesi ML, Morabito S (2011) The complete DNA sequence and analysis of the virulence plasmid and of five additional plasmids carried by Shiga toxin-producing Escherichia coli O26:H11 strain H30. Int J Med Microbiol 301:192–203. doi: 10.1016/j.ijmm.2010.09.002 PubMedCrossRefGoogle Scholar
  55. Friedrich AW, Bielaszewska M, Zhang WL, Pulz M, Kuczius T, Ammon A, Karch H (2002) Escherichia coli harboring Shiga toxin 2 gene variants: frequency and association with clinical symptoms. J Infect Dis 185:74–84. doi: 10.1086/338115 PubMedCrossRefGoogle Scholar
  56. Friedrich AW, Lu S, Bielaszewska M, Prager R, Bruns P, Xu JG, Tschäpe H, Karch H (2006) Cytolethal distending toxin in Escherichia coli O157:H7: spectrum of conservation, structure, and endothelial toxicity. J Clin Microbiols 44:1844–1846. doi: 10.1128/JCM.44.5.1844-1846.2006 CrossRefGoogle Scholar
  57. Fuchs S, Muhldorfer I, Donohue-Rolfe A, Kerenyi M, Emody L, Alexiev R, Nenkov P, Hacker J (1999) Influence of RecA on in vivo virulence and Shiga toxin 2 production in Escherichia coli pathogens. Microb Pathog 27:13–23PubMedCrossRefGoogle Scholar
  58. Fujii J, Kita T, Yoshida S, Takeda T, Kobayashi H, Tanaka N, Ohsato K, Mizuguchi Y (1994) Direct evidence of neuron impairment by oral infection with verotoxin- producing Escherichia coli O157:H-in mitomycin-treated mice. Infect Immun 62:3447–3453PubMedGoogle Scholar
  59. Gao X, Wan F, Mateo K, Callegari E, Wang D, Deng W, Puente J, Li F, Chaussee MS, Finlay BB, Lenardo MJ, Hardwidge PR (2009) Bacterial effector binding to ribosomal protein S3 subverts NF-κB function. PLoS Pathog 5:e1000708. doi: 10.1371/journal.ppat.1000708 PubMedCrossRefGoogle Scholar
  60. Garcia A, Marini RP, Feng Y, Vitsky A, Knox KA, Taylor NS, Schauer DB, Fox JG (2002) A naturally occurring rabbit model of enterohemorrhagic Escherichia coli-induced disease. J Infect Dis 186:1682–1686PubMedCrossRefGoogle Scholar
  61. Garcia A, Bosques CJ, Wishnok JS, Feng Y, Karalius BJ, Butterton JR, Schauer DB, Rogers AB, Fox JG (2006) Renal injury is a consistent finding in Dutch belted rabbits experimentally infected with enterohemorrhagic Escherichia coli. J Infect Dis 193:1125–1134PubMedCrossRefGoogle Scholar
  62. García A, Marini RP, Catalfamo JL, Knox KA, Schauer DB, Rogers AB, Fox JG (2008) Intravenous Shiga toxin 2 promotes enteritis and renal injury characterized by polymorphonuclear leukocyte infiltration and thrombosis in Dutch belted rabbits. Microbes Infect 10:650–656. doi: 10.1016/j.micinf.2008.03.004 PubMedCrossRefGoogle Scholar
  63. Garmendia J, Carlier MF, Egile C, Didry D, Frankel G (2006) Characterization of TccP-mediated N-WASP activation during enterohaemorrhagic Escherichia coli infection. Cell Microbiol 8:1444–1455PubMedCrossRefGoogle Scholar
  64. Glantz PJ, Gyles CL, Greenfield J, Øtskov F (1973) Isolation of Escherichia coli O157 from pigs with colibacillosis in Canada and the United States. Can J Comp Med 37:200–202PubMedGoogle Scholar
  65. Gobert AP, Coste A, Guzman CA, Vareille M, Hindré T, de S.T, Girardeau JP, Martin C (2008) Modulation of chemokine gene expression by Shiga-toxin producing Escherichia coli belonging to various origins and serotypes. Microbes Infect 10:159–165. doi: 10.1016/j.micinf.2007.10.018 PubMedCrossRefGoogle Scholar
  66. Golan L, Gonen E, Yagel S, Rosenshine I, Shpigel NY (2011) Enterohemorrhagic Escherichia coli induce attaching and effacing lesions and hemorrhagic colitis in human and bovine intestinal xenograft models. Dis Model Mech 4:86–94. doi: 10.1242/dmm.005777 PubMedCrossRefGoogle Scholar
  67. Gould LH, Demma L, Jones TF, Hurd S, Vugia DJ, Smith K, Shiferaw B, Segler S, Palmer A, Zansky S, Griffin PM (2009) Hemolytic uremic syndrome and death in persons with Escherichia coli O157:H7 infection, foodborne diseases active surveillance network sites, 2000–2006. Clin Infect Dis 49:1480–1485. doi: 10.1086/644621 PubMedCrossRefGoogle Scholar
  68. Grauke LJ, Kudva IT, Yoon JW, Hunt CW, Williams CJ, Hovde CJ (2002) Gastrointestinal tract location of Escherichia coli O157:H7 in ruminants. Appl Environ Microbiol 68:2269–2277PubMedCrossRefGoogle Scholar
  69. Grys TE, Siegel MB, Lathem WW, Welch RA (2005) The StcE protease contributes to intimate adherence of enterohemorrhagic Escherichia coli O157:H7 to host cells. Infect Immun 73:1295–1303PubMedCrossRefGoogle Scholar
  70. Habdas BJ, Smart J, Kaper JB, Sperandio V (2010) The LysR-type transcriptional regulator QseD alters type three secretion in enterohemorrhagic Escherichia coli and motility in K-12 Escherichia coli. J Bacteriol 192:3699–3712. doi: 10.1128/JB.00382-10 PubMedCrossRefGoogle Scholar
  71. Hayashi T, Makino K, Ohnishi M, Kurokawa K, Ishii K, Yokoyama K, Han CG, Ohtsubo E, Nakayama K, Murata T, Tanaka M, Tobe T, Iida T, Takami H, Honda T, Sasakawa C, Ogasawara N, Yasunaga T, Kuhara S, Shiba T, Hattori M, Shinagawa H (2001) Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res 8:11–22PubMedCrossRefGoogle Scholar
  72. Hedican EB, Medus C, Besser JM, Juni BA, Koziol B, Taylor C, Smith KE (2009) Characteristics of O157 versus non-O157 Shiga toxin-producing Escherichia coli infections in Minnesota, 2000–2006. Clin Infect Dis 49:358–364. doi: 10.1086/600302 PubMedCrossRefGoogle Scholar
  73. Hemrajani C, Marches O, Wiles S, Girard F, Dennis A, Dziva F, Best A, Phillips AD, Berger CN, Mousnier A, Crepin VF, Kruidenier L, Woodward MJ, Stevens MP, La Ragione RM, MacDonald TT, Frankel G (2008) Role of NleH, a type III secreted effector from attaching and effacing pathogens, in colonization of the bovine, ovine, and murine gut. Infect Immun 76:4804–4813. doi: 10.1128/IAI.00742-08 PubMedCrossRefGoogle Scholar
  74. Hemrajani C, Berger CN, Robinson KS, Marchès O, Mousnier A, Frankel G (2010) NleH effectors interact with Bax inhibitor-1 to block apoptosis during enteropathogenic Escherichia coli infection. Proc Natl Acad Sci USA 107:3129–3134. doi: 10.1073/pnas.0911609106 PubMedCrossRefGoogle Scholar
  75. Hermos CR, Janineh M, Han LL, McAdam AJ (2010) Shiga toxin-producing Escherichia coli in children: detection and clinical manifestations of O157:H7 and non-O157:H7 infection. J Clin Microbiol.  10.1128/JCM.02119-10
  76. Herold S, Paton JC, Paton AW (2009) Sab, a novel autotransporter of locus of enterocyte effacement-negative shiga-toxigenic Escherichia coli O113:H21, contributes to adherence and biofilm formation. Infect Immun 77:3234–3243. doi: 10.1128/IAI.00031-09 PubMedCrossRefGoogle Scholar
  77. Ho TD, Davis BM, Ritchie JM, Waldor MK (2008) Type 2 secretion promotes enterohemorrhagic Escherichia coli adherence and intestinal colonization. Infect Immun 76:1858–1865PubMedCrossRefGoogle Scholar
  78. Hurley BP, Jacewicz M, Thorpe CM, Lincicome LL, King AJ, Keusch GT, Acheson DW (1999) Shiga toxins 1 and 2 translocate differently across polarized intestinal epithelial cells. Infect Immun 67:6670–6677PubMedGoogle Scholar
  79. Hussein HS (2007) Prevalence and pathogenicity of Shiga toxin-producing Escherichia coli in beef cattle and their products. J Anim Sci 85:E63–E72. doi: 10.2527/jas.2006-421 PubMedCrossRefGoogle Scholar
  80. Ichinohe N, Ohara-Nemoto Y, Nemoto TK, Kimura S, Ichinohe S (2009) Effects of fosfomycin on Shiga toxin-producing Escherichia coli: quantification of copy numbers of Shiga toxin-encoding genes and their expression levels using real-time PCR. J Med Microbiol 58:971–973. doi: 10.1099/jmm.0.008573-0 PubMedCrossRefGoogle Scholar
  81. Ikeda K, Ida O, Kimoto K, Takatorige T, Nakanishi N, Tatara K (1999) Effect of early fosfomycin treatment on prevention of hemolytic uremic syndrome accompanying Escherichia coli O157:H7 infection. Clin Nephrol 52:357–362PubMedGoogle Scholar
  82. Isogai E, Isogai H, Kimura K, Hayashi S, Kubota T, Fujii N, Takeshi K (1998) Role of tumor necrosis factor alpha in gnotobiotic mice infected with an Escherichia coli O157:H7 strain. Infect Immun 66:197–202PubMedGoogle Scholar
  83. Ito H, Terai A, Kurazono H, Takeda Y, Nishibuchi M (1990) Cloning and nucleotide sequencing of Vero toxin 2 variant genes from Escherichia coli O91:H21 isolated from a patient with the hemolytic uremic syndrome. Microb Pathog 8:47–60PubMedCrossRefGoogle Scholar
  84. Jacewicz M, Clausen H, Nudelman E, Donohue-Rolfe A, Keusch GT (1986) Pathogenesis of Shigella diarrhea XI. Isolation of a Shigella toxin-binding glycolipid from rabbit jejunum and HeLa cells and its identification as globotriaosylceramide. J Exp Med 163:1391–1404PubMedCrossRefGoogle Scholar
  85. Janka A, Bielaszewska M, Dobrindt U, Greune L, Schmidt MA, Karch H (2003) Cytolethal distending toxin gene cluster in enterohemorrhagic Escherichia coli O157:H- and O157:H7: characterization and evolutionary considerations. Infect Immun 71:3634–3638PubMedCrossRefGoogle Scholar
  86. Jeong KI, Tzipori S, Sheoran AS (2010) Shiga toxin 2-specific but not Shiga toxin 1-specific human monoclonal antibody protects piglets challenged with enterohemorrhagic Escherichia coli producing Shiga toxin 1 and Shiga toxin 2. J Infect Dis 201:1081–1083. doi: 10.1086/651198 PubMedCrossRefGoogle Scholar
  87. Jerse AE, Yu J, Tall BD, Kaper JB (1990) A genetic locus of enteropathogenic Escherichia coli necessary for the production of attaching and effacing lesions on tissue culture cells. Proc Natl Acad Sci USA 87:7839–7843PubMedCrossRefGoogle Scholar
  88. Johansen BK, Wasteson Y, Granum PE, Brynestad S (2001) Mosaic structure of Shiga-toxin-2-encoding phages isolated from Escherichia coli O157:H7 indicates frequent gene exchange between lambdoid phage genomes. Microbiology 147:1929–1936PubMedGoogle Scholar
  89. Judge NA, Mason HS, O’Brien AD (2004) Plant cell-based intimin vaccine given orally to mice primed with intimin reduces time of Escherichia coli O157:H7 shedding in feces. Infect Immun 72:168–175PubMedCrossRefGoogle Scholar
  90. Kaneko K, Kiyokawa N, Ohtomo Y, Nagaoka R, Yamashiro Y, Taguchi T, Mori T, Fujimoto J, Takeda T (2001) Apoptosis of renal tubular cells in Shiga-toxin-mediated hemolytic uremic syndrome. Nephron 87:182–185PubMedCrossRefGoogle Scholar
  91. Kang G, Pulimood AB, Koshi R, Hull A, Acheson D, Rajan P, Keusch GT, Mathan VI, Mathan MM (2001) A monkey model for enterohemorrhagic Escherichia coli infection. J Infect Dis 184:206–210PubMedCrossRefGoogle Scholar
  92. Käppeli U, Hächler H, Giezendanner N, Cheasty T, Stephan R (2010) Shiga toxin-producing Escherichia coli O157 associated with human infections in Switzerland, 2000-2009. Epidemiol Infect:1–8. doi: 10.1017/S0950268810002190
  93. Karch H, Bielaszewska M (2001) Sorbitol-fermenting Shiga toxin-producing Escherichia coli O157:H- strains: epidemiology, phenotypic and molecular characteristics, and microbiological diagnosis. J Clin Microbiol 39:2043–2049. doi: 10.1128/JCM.39.6.2043-2049.2001 PubMedCrossRefGoogle Scholar
  94. Karch H, Goroncy-Termes P, Opferkuch W, Kroll H-P, O’Brien A (1985) Subinhibitory concentrations of antibiotics modulate amount of Shiga-like toxin produced by Escherichia coli. In: Adam D, Hahn H, Opferkuch W (eds) The influence of antibiotics on the host-parasite relationship II. Springer, Berlin, pp 239–245CrossRefGoogle Scholar
  95. Karmali MA, Mascarenhas M, Shen S, Ziebell K, Johnson S, Reid-Smith R, Isaac-Renton J, Clark C, Rahn K, Kaper JB (2003) Association of genomic O island 122 of Escherichia coli EDL 933 with verocytotoxin-producing Escherichia coli seropathotypes that are linked to epidemic and/or serious disease. J Clin Microbiol 41:4930–4940PubMedCrossRefGoogle Scholar
  96. Karpman D, Connell H, Svensson M, Scheutz F, Alm P, Svanborg C (1997) The role of lipopolysaccharide and Shiga-like toxin in a mouse model of Escherichia coli O157:H7 infection. J Infect Dis 175:611–620PubMedCrossRefGoogle Scholar
  97. Karpman D, Hakansson A, Perez MT, Isaksson C, Carlemalm E, Caprioli A, Svanborg C (1998) Apoptosis of renal cortical cells in the hemolytic-uremic syndrome: in vivo and in vitro studies. Infect Immun 66:636–644PubMedGoogle Scholar
  98. Keenan KP, Sharpnack DD, Collins H, Formal SB, O’Brien AD (1986) Morphologic evaluation of the effects of Shiga toxin and E. coli Shiga-like toxin on the rabbit intestine. Am J Pathol 125:69–80PubMedGoogle Scholar
  99. 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 17:3404–3414PubMedCrossRefGoogle Scholar
  100. Kendall MM, Rasko DA, Sperandio V (2010) The LysR-type regulator QseA regulates both characterized and putative virulence genes in enterohaemorrhagic Escherichia coli O157:H7. Mol Microbiol 76:1306–1321. doi: 10.1111/j.1365-2958.2010.07174.x PubMedCrossRefGoogle Scholar
  101. Kenny B, DeVinney R, Stein M, Reinscheid DJ, Frey EA, Finlay BB (1997) Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell 91:511–520PubMedCrossRefGoogle Scholar
  102. Kimura T, Co MS, Vasquez M, Wei S, Xu H, Tani S, Sakai Y, Kawamura T, Matsumoto Y, Nakao H, Takeda T (2002) Development of humanized monoclonal antibody TMA-15 which neutralizes Shiga toxin 2. Hybrid Hybridomics 21:161–168PubMedCrossRefGoogle Scholar
  103. King T, Lucchini S, Hinton JC, Gobius K (2010) Transcriptomic analysis of Escherichia coli O157:H7 and K-12 cultures exposed to inorganic and organic acids in stationary phase reveals acidulant-and strain-specific acid tolerance responses. Appl Environ Microbiol 76:6514–6528. doi: 10.1128/AEM.02392-09 PubMedCrossRefGoogle Scholar
  104. Kokai-Kun JF, Melton-Celsa AR, O’Brien AD (2000) Elastase in intestinal mucus enhances the cytotoxicity of Shiga toxin type 2d. J Biol Chem 275:3713–3721PubMedCrossRefGoogle Scholar
  105. Konadu E, Robbins JB, Shiloach J, Bryla DA, Szu SC (1994) Preparation, characterization, and immunological properties in mice of Escherichia coli O157 O-specific polysaccharide-protein conjugate vaccines. Infect Immun 62:5048–5054PubMedGoogle Scholar
  106. Konadu EY, Parke JC Jr, Tran HT, Bryla DA, Robbins JB, Szu SC (1998) Investigational vaccine for Escherichia coli O157: phase 1 study of O157 O-specific polysaccharide-Pseudomonas aeruginosa recombinant exoprotein A conjugates in adults. J Infect Dis 177:383–387PubMedCrossRefGoogle Scholar
  107. Konowalchuk J, Speirs JI, Stavric S (1977) Vero response to a cytotoxin of Escherichia coli. Infect Immun 18:775–779PubMedGoogle Scholar
  108. Kresse AU, Rienäcker I, Valle AM, Steinrück H, Claus H, Payne SM, Tschäpe H, Williams PH, Reissbrodt R (2007) Enterohaemorrhagic Escherichia coli O157 and non-O157 serovars differ in their mechanisms for iron supply. Int J Med Microbiol 297:9–15. doi: 10.1016/j.ijmm.2006.11.002 PubMedCrossRefGoogle Scholar
  109. Kurioka T, Yunou Y, Kita E (1998) Enhancement of susceptibility to Shiga toxin-producing Escherichia coli O157:H7 by protein calorie malnutrition in mice. Infect Immun 66:1726–1734PubMedGoogle Scholar
  110. Lariviére SR, Lallier (1976) Escherichia coli strains isolated from diarrheic piglets in the Province of Quebec. Can J Comp Med 40:190–197PubMedGoogle Scholar
  111. Ledesma MA, Ochoa SA, Cruz A, Rocha-Ramirez LM, Mas-Oliva J, Eslava CA, Girón JA, Xicohtencatl-Cortes J (2010) The hemorrhagic coli pilus (HCP) of Escherichia coli O157:H7 is an inducer of proinflammatory cytokine secretion in intestinal epithelial cells. PLoSONE. 5:12127. doi: 10.1371/journal.pone.0012127
  112. Leotta GA, Miliwebsky ES, Chinen I, Espinosa EM, Azzopardi K, Tennant SM, Robins-Browne RM, Rivas M (2008) Characterisation of Shiga toxin-producing Escherichia coli O157 strains isolated from humans in Argentina, Australia and New Zealand. BMC Microbiol 8:46. doi: 10.1186/1471-2180-8-46
  113. Levine MM (1987) Escherichia coli that cause diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherent. J Infect Dis 155:377–389PubMedCrossRefGoogle Scholar
  114. Lim JY, Yoon J, Hovde CJ (2010) A Brief Overview of Escherichia coli O157:H7 and Its Plasmid O157. J Microbiol Biotechnol 20:5–14. doi: 10.4014/jmb.0908.08007 PubMedGoogle Scholar
  115. Lindberg AA, Brown JE, Stromberg N, Westling-Ryd M, Schultz JE, Karlsson KA (1987) Identification of the carbohydrate receptor for Shiga toxin produced by Shigella dysenteriae type 1. J Biol Chem 262:1779–1785PubMedGoogle Scholar
  116. Lindgren SW, Melton AR, O’Brien AD (1993) Virulence of enterohemorrhagic Escherichia coli O91:H21 clinical isolates in an orally infected mouse model. Infect Immun 61:3832–3842PubMedGoogle Scholar
  117. Lindgren SW, Samuel JE, Schmitt CK, O’Brien AD (1994) The specific activities of Shiga-like toxin type II (SLT-II) and SLT-II-related toxins of enterohemorrhagic Escherichia coli differ when measured by Vero cell cytotoxicity but not by mouse lethality. Infect Immun 62:623–631PubMedGoogle Scholar
  118. Livny J, Friedman DI (2004) Characterizing spontaneous induction of Stx encoding phages using a selectable reporter system. Mol Microbiol 51:1691–1704. doi: 10.1111/j.1365-2958.2003.03934.x PubMedCrossRefGoogle Scholar
  119. Low JC, McKendrick IJ, McKechnie C, Fenlon D, Naylor SW, Currie C, Smith DG, Allison L, Gally DL (2005) Rectal carriage of enterohemorrhagic Escherichia coli O157 in slaughtered cattle. Appl Environ Microbiol 71:93–97. doi: 10.1128/AEM.71.1.93-97.2005 PubMedCrossRefGoogle Scholar
  120. Makino K, Ishii K, Yasunaga T, Hattori M, Yokoyama K, Yutsudo CH, Kubota Y, Yamaichi Y, Iida T, Yamamoto K, Honda T, Han CG, Ohtsubo E, Kasamatsu M, Hayashi T, Kuhara S, Shinagawa H (1998) Complete nucleotide sequences of 93-kb and 3.3-kb plasmids of an enterohemorrhagic Escherichia coli O157:H7 derived from Sakai outbreak. DNA Res 5:1–9PubMedCrossRefGoogle Scholar
  121. Manning SD, Motiwala AS, Springman AC, Qi W, Lacher DW, Ouellette LM, Mladonicky JM, Somsel P, Rudrik JT, Dietrich SE, Zhang W, Swaminathan B, Alland D, Whittam TS (2008) Variation in virulence among clades of Escherichia coli O157:H7 associated with disease outbreaks. Proc Natl Acad Sci USA 105:4868–4873PubMedCrossRefGoogle Scholar
  122. McKee ML, Melton-Celsa AR, Moxley RA, Francis DH, O’Brien AD (1995) Enterohemorrhagic Escherichia coli O157:H7 requires intimin to colonize the gnotobiotic pig intestine and to adhere to HEp-2 cells. Infect Immun 63:3739–3744PubMedGoogle Scholar
  123. Melton-Celsa AR, Darnell SC, O’Brien AD (1996) Activation of Shiga-like toxins by mouse and human intestinal mucus correlates with virulence of enterohemorrhagic Escherichia coli O91:H21 isolates in orally infected, streptomycin-treated mice. Infect Immun 64:1569–1576PubMedGoogle Scholar
  124. Melton-Celsa AR, Smith MJ, O’Brien AD (2005) Shiga toxins: potent poisons, pathogenicity determinants, and pharmacological agents. In: Curtiss III R (ed) EcoSal-Escherichia coli and Salmonella: Cellular and molecular biology (Online), 2nd edn. ASM Press, Washington, D.CGoogle Scholar
  125. Melton-Celsa AR, Robinson CM, Smith MJ, O’Brien AD (2007) Shiga toxins (Stxs): multifaceted pathogenicity determinants. In: Brogden KA, Minion FC, Cornick N, Stanton TB, Zhang Q, Nolan LK, Wannemuehler MJ (eds) Virulence mechanisms of bacterial pathogens, 4th edn. ASM Press, Washington, DC, pp 239–251Google Scholar
  126. Michino H, Araki K, Minami S, Takaya S, Sakai N, Miyazaki M, Ono A, Yanagawa H (1999) Massive outbreak of Escherichia coli O157:H7 infection in schoolchildren in Sakai City, Japan, associated with consumption of white radish sprouts. Am J Epidemiol 150:787–796PubMedCrossRefGoogle Scholar
  127. Miller SI, Kukral AM, Mekalanos JJ (1989) A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci USA 86:5054–5058PubMedCrossRefGoogle Scholar
  128. Mohawk KL, O’Brien AD (2011) Mouse models of Escherichia coli O157:H7 infection and Shiga toxin injection. J Biomed Biotechnol 2011:258185. doi: 10.1155/2011/258185
  129. Mohawk KL, Melton-Celsa AR, Zangari T, Carroll EE, O’Brien AD (2010) Pathogenesis of Escherichia coli O157:H7 strain 86–24 following oral infection of BALB/c mice with an intact commensal flora. Microb Pathog 48:131–142. doi: 10.1016/j.micpath.2010.01.003 PubMedCrossRefGoogle Scholar
  130. Mukherjee J, Chios K, Fishwild D, Hudson D, O’Donnell S, Rich SM, Donohue-Rolfe A, Tzipori S (2002a) Human Stx2-specific monoclonal antibodies prevent systemic complications of Escherichia coli O157:H7 infection. Infect Immun 70:612–619PubMedCrossRefGoogle Scholar
  131. Mukherjee J, Chios K, Fishwild D, Hudson D, O’Donnell S, Rich SM, Donohue-Rolfe A, Tzipori S (2002b) Production and characterization of protective human antibodies against Shiga toxin 1. Infect Immun 70:5896–5899PubMedCrossRefGoogle Scholar
  132. Mulvey GL, Marcato P, Kitov PI, Sadowska J, Bundle DR, Armstrong GD (2003) Assessment in mice of the therapeutic potential of tailored, multivalent Shiga toxin carbohydrate ligands. J Infect Dis 187:640–649PubMedCrossRefGoogle Scholar
  133. Nagano K, Taguchi K, Hara T, Yokoyama S, Kawada K, Mori H (2003) Adhesion and colonization of enterohemorrhagic Escherichia coli O157:H7 in cecum of mice. Microbiol Immunol 47:125–132PubMedGoogle Scholar
  134. Naylor SW, Low JC, Besser TE, Mahajan A, Gunn GJ, Pearce MC, McKendrick IJ, Smith DG, Gally DL (2003) Lymphoid follicle-dense mucosa at the terminal rectum is the principal site of colonization of enterohemorrhagic Escherichia coli O157:H7 in the bovine host. Infect Immun 71:1505–1512PubMedCrossRefGoogle Scholar
  135. Neisser M, Shiga K (1903) Ueber freie recptoren von Typhu––und dysenterue-bazillen und ueber das dysenterie toxin. Dtsch Med Wochenschr 29:61–62CrossRefGoogle Scholar
  136. Nishikawa K, Matsuoka K, Kita E, Okabe N, Mizuguchi M, Hino K, Miyazawa S, Yamasaki C, Aoki J, Takashima S, Yamakawa Y, Nishijima M, Terunuma D, Kuzuhara H, Natori Y (2002) A therapeutic agent with oriented carbohydrates for treatment of infections by Shiga toxin-producing Escherichia coli O157:H7. Proc Natl Acad Sci USA 99:7669–7674PubMedCrossRefGoogle Scholar
  137. Obata F, Tohyama K, Bonev AD, Kolling GL, Keepers TR, Gross LK, Nelson MT, Sato S, Obrig TG (2008) Shiga toxin 2 affects the central nervous system through receptor globotriaosylceramide localized to neurons. J Infect Dis 198:1398–1406PubMedCrossRefGoogle Scholar
  138. Ogura Y, Ooka T, Iguchi A, Toh H, Asadulghani M, Oshima K, Kodama T, Abe H, Nakayama K, Kurokawa K, Tobe T, Hattori M, Hayashi T (2009) Comparative genomics reveal the mechanism of the parallel evolution of O157 and non-O157 enterohemorrhagic Escherichia coli. Proc Natl Acad Sci USA 106:17939–17944. doi: 10.1073/pnas.0903585106 PubMedCrossRefGoogle Scholar
  139. O’Reilly KM, Low JC, Denwood MJ, Gally DL, Evans J, Gunn GJ, Mellor DJ, Reid SW, Matthews L (2010) Associations between the presence of virulence determinants and the epidemiology and ecology of zoonotic Escherichia coli. Appl Environ Microbiol 76:8110–8116. doi: 10.1128/AEM.01343-10 PubMedCrossRefGoogle Scholar
  140. Panda A, Tatarov I, Melton-Celsa AR, Kolappaswamy K, Kriel EH, Petkov D, Coksaygan T, Livio S, McLeod CG, Nataro JP, O’Brien AD, DeTolla LJ (2010) Escherichia coli O157:H7 infection in Dutch belted and New Zealand white rabbits. Comp Med 60:31–37PubMedGoogle Scholar
  141. Paton AWJC, Paton (2010) Escherichia coli subtilase cytotoxin. Toxins (Basel) 2:215–228. doi: 10.3390/toxins2020215 CrossRefGoogle Scholar
  142. Paton AW, Srimanote P, Woodrow MC, Paton JC (2001) Characterization of Saa, a novel autoagglutinating adhesin produced by locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli strains that are virulent for humans. Infect Immun 69:6999–7009PubMedCrossRefGoogle Scholar
  143. Paton AW, Srimanote P, Talbot UM, Wang H, Paton JC (2004) A new family of potent AB(5) cytotoxins produced by Shiga toxigenic Escherichia coli. J Exp Med 200:35–46PubMedCrossRefGoogle Scholar
  144. Paton AW, Bddoe T, Thorpe CM, Whisstock JC, Wilce MCJ, Rossjohn J, Talbot UM, Paton JC (2006) AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP. Nature 443:548–552PubMedCrossRefGoogle Scholar
  145. Perna NT, Plunkett G III, Burland V, Mau B, Glasner JD, Rose DJ, Mayhew GF, Evans PS, Gregor J, Kirkpatrick HA, Pósfai G, Hackett J, Klink S, Boutin A, Shao Y, Miller L, Grotbeck EJ, Davis NW, Lim A, Dimalanta ET, Potamousis KD, Apodaca J, Anantharaman TS, Lin J, Yen G, Schwartz DC, Welch RA, Blattner FR (2001) Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409:529–533PubMedCrossRefGoogle Scholar
  146. Philpott DJ, Ackerley CA, Kiliaan AJ, Karmali MA, Perdue MH, Sherman PM (1997) Translocation of verotoxin-1 across T84 monolayers: mechanism of bacterial toxin penetration of epithelium. Am J Physiol 273:G1349–G1358PubMedGoogle Scholar
  147. Pinyon RA, Paton JC, Paton AW, Botten JA, Morona R (2004) Refinement of a therapeutic shiga toxin-binding probiotic for human trials. J Infect Dis 189:1547–1555PubMedCrossRefGoogle Scholar
  148. Poirier K, Faucher SP, Béland M, Brousseau R, Gannon V, Martin C, Harel J, Daigle F (2008) Escherichia coli O157:H7 survives within human macrophages: global gene expression profile and involvement of the Shiga toxins. Infect Immun 76:4814–4822PubMedCrossRefGoogle Scholar
  149. Potter ME, Kaufmann AF, Thomason BM, Blake PA, Farmer JJ III (1985) Diarrhea due to Escherichia coli O157:H7 in the infant rabbit. J Infect Dis 152:1341–1343PubMedCrossRefGoogle Scholar
  150. Ptashne M (2004) A Genetic Switch. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
  151. Puttamreddy SN, Cornick A, Minion FC (2010) Genome-wide transposon mutagenesis reveals a role for pO157 genes in biofilm development in Escherichia coli O157:H7 EDL933. Infect Immun doi: 10.1128/IAI.00156-10
  152. Raife T, Friedman KD, Fenwick B (2004) Lepirudin prevents lethal effects of Shiga toxin in a canine model. Thromb Haemost 92:387–393. doi: 10.1267/THRO04080387;04080387 PubMedGoogle Scholar
  153. Richardson SE, Rotman TA, Jay V, Smith CR, Becker LE, Petric M, Olivieri NF, Karmali MA (1992) Experimental verocytotoxemia in rabbits. Infect Immun 60:4154–4167PubMedGoogle Scholar
  154. Riley LW, Remis RS, Helgerson SD, McGee HB, Wells JG, Davis BR, Hebert RJ, Olcott ES, Johnson LM, Hargrett NT, Blake PA, Cohen ML (1983) Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med 308:681–685PubMedCrossRefGoogle Scholar
  155. Ritchie JMMK, Waldor (2005) The locus of enterocyte effacement-encoded effector proteins all promote enterohemorrhagic Escherichia coli pathogenicity in infant rabbits. Infect Immun 73:1466–1474. doi: 10.1128/IAI.73.3.1466-1474.2005 PubMedCrossRefGoogle Scholar
  156. Ritchie JM, Thorpe CM, Rogers AB, Waldor MK (2003) Critical roles for stx2, eae, and tir in enterohemorrhagic Escherichia coli-induced diarrhea and intestinal inflammation in infant rabbits. Infect Immun 71:7129–7139PubMedCrossRefGoogle Scholar
  157. Robinson CM, Sinclair JF, Smith MJ, O’Brien AD (2006) Shiga toxin of enterohemorrhagic Escherichia coli type O157:H7 promotes intestinal colonization. Proc Natl Acad Sci USA 103:9667–9672PubMedCrossRefGoogle Scholar
  158. Sargeant JM, Amezcua, Rajic A, Waddell L (2007) Pre-harvest interventions to reduce the shedding of E. coli O157 in the faeces of weaned domestic ruminants: a systematic review. Zoonoses Public Health 54:260–277. doi: 10.1111/j.1863-2378.2007.01059.x PubMedCrossRefGoogle Scholar
  159. Sauter KA, Melton-Celsa AR, Larkin K, Troxell ML, O’Brien AD, Magun BE (2008) Mouse model of hemolytic-uremic syndrome caused by endotoxin-free Shiga toxin 2 (Stx2) and protection from lethal outcome by anti-Stx2 antibody. Infect Immun 76:4469–4478PubMedCrossRefGoogle Scholar
  160. Scallan E, Hoekstra RM, Angulo FJ, Tauxe RV, Widdowson MA, Roy SL, Jones JL, Griffin PM (2011) Foodborne illness acquired in the United States–major pathogens. Emerg Infect Dis 17:7–15PubMedGoogle Scholar
  161. Schmitt CK, McKee ML, O’Brien AD (1991) Two copies of Shiga-like toxin II-related genes common in enterohemorrhagic Escherichia coli strains are responsible for the antigenic heterogeneity of the O157:H- strain E32511. Infect Immun 59:1065–1073PubMedGoogle Scholar
  162. Serna AEC, Boedeker (2008) Pathogenesis and treatment of Shiga toxin-producing Escherichia coli infections. Curr Opin Gastroenterol 24:38–47PubMedCrossRefGoogle Scholar
  163. Sheng H, Lim JY, Knecht HJ, Li J, Hovde CJ (2006) Role of Escherichia coli O157:H7 virulence factors in colonization at the bovine terminal rectal mucosa. Infect Immun 74:4685–4693PubMedCrossRefGoogle Scholar
  164. Sinclair JF, O’Brien AD (2002) Cell surface-localized nucleolin is a eukaryotic receptor for the adhesin intimin-gamma of enterohemorrhagic Escherichia coli O157:H7. J Biol Chem 277:2876–2885PubMedCrossRefGoogle Scholar
  165. Sjogren R, Neill R, Rachmilewitz D, Fritz D, Newland J, Sharpnack D, Colleton C, Fondacaro J, Gemski P, Boedeker E (1994) Role of Shiga-like toxin I in bacterial enteritis: comparison between isogenic Escherichia coli strains induced in rabbits. Gastroenterology 106:306–317PubMedGoogle Scholar
  166. Smith DR, Moxley RA, Peterson RE, Klopfenstein TJ, Erickson GE, Bretschneider G, Berberov EM, Clowser S (2009) A two-dose regimen of a vaccine against type III secreted proteins reduced Escherichia coli O157:H7 colonization of the terminal rectum in beef cattle in commercial feedlots. Foodborne Pathog Dis 6:155–161. doi: 10.1089/fpd.2008.0136 PubMedCrossRefGoogle Scholar
  167. Sugatani J, Komiyama N, Mochizuki T, Hoshino M, Miyamoto D, Igarashi T, Hoshi S, Miwa M (2002) Urinary concentrating defect in rats given Shiga toxin: elevation in urinary AQP2 level associated with polyuria. Life Sci 71:171–189. Google Scholar
  168. Suri, RS, Mahon JL, Clark WF, Moist LM, Salvadori M, Garg AX (2009) Relationship between Escherichia coli O157:H7 and diabetes mellitus. Kidney Int Suppl S44-S46. doi: 10.1038/ki.2008.619
  169. Tarr PI, Bilge SS, Vary JC Jr, Jelacic S, Habeeb RL, Ward TR, Baylor MR, Besser TE (2000) Iha: a novel Escherichia coli O157:H7 adherence-conferring molecule encoded on a recently acquired chromosomal island of conserved structure. Infect Immun 68:1400–1407PubMedCrossRefGoogle Scholar
  170. Tatsuno I, Horie M, Abe H, Miki T, Makino K, Shinagawa H, Taguchi H, Kamiya S, Hayashi T, Sasakawa C (2001) toxB gene on pO157 of enterohemorrhagic Escherichia coli O157:H7 is required for full epithelial cell adherence phenotype. Infect Immun 69:6660–6669PubMedCrossRefGoogle Scholar
  171. Taylor CM, Williams JM, Lote CJ, Howie AJ, Thewles A, Wood JA, Milford DV, Raafat F, Chant I, Rose PE (1999a) A laboratory model of toxin-induced hemolytic uremic syndrome. Kidney Int 55:1367–1374PubMedCrossRefGoogle Scholar
  172. Taylor FB Jr, Tesh VL, DeBault L, Li A, Chang AC, Kosanke SD, Pysher TJ, Siegler RL (1999b) Characterization of the baboon responses to Shiga-like toxin: descriptive study of a new primate model of toxic responses to Stx-1. Am J Pathol 154:1285–1299PubMedCrossRefGoogle Scholar
  173. te Loo DM, Monnens LA, van Den LP, Heuvel MC, Gubler MM, Kockx (2001) Detection of apoptosis in kidney biopsies of patients with D + hemolytic uremic syndrome. Pediatr Res 49:413–416PubMedCrossRefGoogle Scholar
  174. Teel LD, Melton-Celsa AR, Schmitt CK, O’Brien AD (2002) One of two copies of the gene for the activatable Shiga toxin type 2d in Escherichia coli O91:H21 strain B2F1 is associated with an inducible bacteriophage. Infect Immun 70:4282–4291PubMedCrossRefGoogle Scholar
  175. Tesh VL (2010) Induction of apoptosis by Shiga toxins. Future Microbiol 5:431–453. doi: 10.2217/fmb.10.4 PubMedCrossRefGoogle Scholar
  176. Teunis P, Ogden FID, Strachan NJ (2008) Hierarchical dose response of E. coli O157:H7 from human outbreaks incorporating heterogeneity in exposure. Epidemiol Infect 136:761-770. doi: 10.1017/S0950268807008771 Google Scholar
  177. Thomson DU, Loneragan GH, Thornton AB, Lechtenberg KF, Emery DA, Burkhardt DT, Nagaraja TG (2009) Use of a siderophore receptor and porin proteins-based vaccine to control the burden of Escherichia coli O157:H7 in feedlot cattle. Foodborne Pathog Dis 6:871–877. doi: 10.1089/fpd.2009.0290 PubMedCrossRefGoogle Scholar
  178. Tilden J Jr, Young W, McNamara AM, Custer C, Boesel B, Lambert-Fair MA, Majkowski J, Vugia D, Werner SB, Hollingsworth J, Morris JG Jr (1996) A new route of transmission for Escherichia coli: infection from dry fermented salami. Am J Public Health 86:1142–1145PubMedCrossRefGoogle Scholar
  179. Tobe T, Beatson SA, Taniguchi H, Abe H, Bailey CM, Fivian A, Younis R, Matthews S, Marches O, Frankel G, Hayashi T, Pallen MJ (2006) An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination. Proc Natl Acad Sci USA 103:14941–14946PubMedCrossRefGoogle Scholar
  180. Toma C, Martinez EE, Song T, Miliwebsky E, Chinen I, Iyoda S, Iwanaga M, Rivas M (2004) Distribution of putative adhesins in different seropathotypes of Shiga toxin-producing Escherichia coli. J Clin Microbiol 42:4937–4946. doi: 10.1128/JCM.42.11.4937-4946.2004 PubMedCrossRefGoogle Scholar
  181. Torres AG, Zhou X, Kaper JB (2005) Adherence of diarrheagenic Escherichia coli strains to epithelial cells. Infect Immun 73:18–29PubMedCrossRefGoogle Scholar
  182. Toth I, Cohen ML, Rumschlag HS, Riley LW, White EH, Carr JH, Bond WW, Wachsmuth IK (1990) Influence of the 60-megadalton plasmid on adherence of Escherichia coli O157:H7 and genetic derivatives. Infect Immun 58:1223–1231PubMedGoogle Scholar
  183. Trachtman H, Cnaan A, Christen E, Gibbs K, Zhao S, Acheson DW, Weiss R, Kaskel FJ, Spitzer A, Hirschman GH (2003) Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome in children: a randomized controlled trial. JAMA 290:1337–1344PubMedCrossRefGoogle Scholar
  184. Tree JJ, Wolfson EB, Wang D, Roe AJ, Gally DL (2009) Controlling injection: regulation of type III secretion in enterohaemorrhagic Escherichia coli. Trends Microbiol 17:361–370. doi: 10.1016/j.tim.2009.06.001 PubMedCrossRefGoogle Scholar
  185. Tyler JS, Mills MJ, Friedman DI (2004) The operator and early promoter region of the Shiga toxin type 2-encoding bacteriophage 933 W and control of toxin expression. J Bacteriol 186:7670–7679. doi: 10.1128/JB.186.22.7670-7679.2004 PubMedCrossRefGoogle Scholar
  186. Tzipori S, Wachsmuth IK, Chapman C, Birden R, Brittingham J, Jackson C, Hogg J (1986) The pathogenesis of hemorrhagic colitis caused by Escherichia coli O157:H7 in gnotobiotic piglets. J Infect Dis 154:712–716PubMedCrossRefGoogle Scholar
  187. Tzipori S, Wachsmuth KI, Smithers J, Jackson C (1988) Studies in gnotobiotic piglets on non-O157:H7 Escherichia coli serotypes isolated from patients with hemorrhagic colitis. Gastroenterology 94:590–597PubMedGoogle Scholar
  188. Tzipori S, Gibson R, Montanaro J (1989) Nature and distribution of mucosal lesions associated with enteropathogenic and enterohemorrhagic Escherichia coli in piglets and the role of plasmid-mediated factors. Infect Immun 57:1142–1150PubMedGoogle Scholar
  189. Tzipori S, Sheoran A, Akiyoshi D, Donohue-Rolfe A, Trachtman H (2004) Antibody therapy in the management of shiga toxin-induced hemolytic uremic syndrome. Clin Microbiol Rev 17:926–941PubMedCrossRefGoogle Scholar
  190. Uchida H, Kiyokawa N, Horie H, Fujimoto J, Takeda T (1999) The detection of Shiga toxins in the kidney of a patient with hemolytic uremic syndrome. Pediatr Res 45:133–137PubMedCrossRefGoogle Scholar
  191. Unkmeir AH, Schmidt (2000) Structural analysis of phage-borne stx genes and their flanking sequences in shiga toxin-producing Escherichia coli and Shigella dysenteriae type 1 strains. Infect Immun 68:4856–4864PubMedCrossRefGoogle Scholar
  192. Vingadassalom D, Campellone KG, Brady MJ, Skehan B, Battle SE, Robbins D, Kapoor A, Hecht G, Snapper SB, Leong JM (2010) Enterohemorrhagic E coli requires N-WASP for efficient type III translocation but not for EspFU-mediated actin pedestal formation. PLoS Pathog 6:1–16. doi: 10.1371/journal.ppat.1001056 CrossRefGoogle Scholar
  193. Wadolkowski EA, Burris JA, O’Brien AD (1990a) Mouse model for colonization and disease caused by enterohemorrhagic Escherichia coli O157:H7. Infect Immun 58:2438–2445PubMedGoogle Scholar
  194. Wadolkowski EA, Sung LM, Burris JA, Samuel JE, O’Brien AD (1990b) Acute renal tubular necrosis and death of mice orally infected with Escherichia coli strains that produce Shiga-like toxin type II. Infect Immun 58:3959–3965PubMedGoogle Scholar
  195. Wagner PL, Livny J, Neely MN, Acheson DW, Friedman DI, Waldor MK (2002) Bacteriophage control of Shiga toxin 1 production and release by Escherichia coli. Mol Microbiol 44:957–970PubMedCrossRefGoogle Scholar
  196. Walters MV, Sperandio (2006) Quorum sensing in Escherichia coli and Salmonella. Int J Med Microbiol 296:125–131. doi: 10.1016/j.ijmm.2006.01.041 PubMedCrossRefGoogle Scholar
  197. Wang H, Paton JC, Paton AW (2007) Pathologic changes in mice induced by subtilase cytotoxin, a potent new Escherichia coli AB5 toxin that targets the endoplasmic reticulum. J Infect Dis 196:1093–1101PubMedCrossRefGoogle Scholar
  198. Wells JG, Davis BR, Wachsmuth IK, Riley LW, Remis RS, Sokolow R, Morris GK (1983) Laboratory investigation of hemorrhagic colitis outbreaks associated with a rare Escherichia coli serotype. J Clin Microbiol 18:512–520PubMedGoogle Scholar
  199. Whittam TS, Wachsmuth IK, Wilson RA (1988) Genetic evidence of clonal descent of Escherichia coli O157:H7 associated with hemorrhagic colitis and hemolytic uremic syndrome. J Infect Dis 157:1124–1133PubMedCrossRefGoogle Scholar
  200. Woods JB, Schmitt CK, Darnell SC, Meysick KC, O’Brien AD (2002) Ferrets as a model system for renal disease secondary to intestinal infection with Escherichia coli O157:H7 and other Shiga toxin-producing E. coli. J Infect Dis 185:550–554PubMedCrossRefGoogle Scholar
  201. Yamagami S, Motoki M, Kimura T, Izumi H, Takeda T, Katsuura Y, Matsumoto Y (2001) Efficacy of postinfection treatment with anti-Shiga toxin (Stx) 2 humanized monoclonal antibody TMA-15 in mice lethally challenged with Stx-producing Escherichia coli. J Infect Dis 184:738–742PubMedCrossRefGoogle Scholar
  202. Yamamoto ET, Mizuno M, Nishikawa K, Miyazawa S, Zhang L, Matsuo S, Natori Y (2005) Shiga toxin 1 causes direct renal injury in rats. Infect Immun 73:7099–7106PubMedCrossRefGoogle Scholar
  203. Yen, H, Ooka T, Iguchi A, Hayashi T, Sugimoto N, Tobe T (2010) NleC, a type III secretion protease, compromises NF-κB activation by targeting p65/RelA. PLoS Pathog 6:e1001231. doi: 10.1371/journal.ppat.1001231 PubMedCrossRefGoogle Scholar
  204. Yin X, Chambers JR, Wheatcroft R, Johnson RP, Zhu J, Liu B, Gyles CL (2009) Adherence of Escherichia coli O157:H7 mutants in vitro and in ligated pig intestines. Appl Environ Microbiol 75:4975–4983. doi: 10.1128/AEM.00297-09 PubMedCrossRefGoogle Scholar
  205. Zhang X, McDaniel AD, Wolf LE, Keusch GT, Waldor MK, Acheson DW (2000) Quinolone antibiotics induce Shiga toxin-encoding bacteriophages, toxin production, and death in mice. J Infect Dis 181:664–670PubMedCrossRefGoogle Scholar
  206. Zheng Y, Valdez PA, Danilenko DM, Hu Y, Sa SM, Gong Q, Abbas AR, Modrusan Z, Ghilardi N, de Sauvage FJ, Ouyang W (2008) Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14:282–289. doi: 10.1038/nm1720 PubMedCrossRefGoogle Scholar
  207. Zoja C, Buelli S, Morigi M (2010) Shiga toxin-associated hemolytic uremic syndrome: pathophysiology of endothelial dysfunction. Pediatr Nephrol 25:2231–2240. doi: 10.1007/s00467-010-1522-1 PubMedCrossRefGoogle Scholar
  208. Zotta E, Lago N, Ochoa F, Repetto HA, Ibarra C (2008) Development of an experimental hemolytic uremic syndrome in rats. Pediatr Nephrol 23:559–567PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Angela Melton-Celsa
    • 1
  • Krystle Mohawk
    • 1
  • Louise Teel
    • 1
  • Alison O’Brien
    • 1
    Email author
  1. 1.BethesdaUSA

Personalised recommendations