J Vet Sci.  2008 Sep;9(3):219-231. 10.4142/jvs.2008.9.3.219.

All blood, No stool: enterohemorrhagic Escherichia coli O157:H7 infection

• Yoon JW
• Hovde CJ

• KMID: 1718574
• DOI: http://doi.org/10.4142/jvs.2008.9.3.219

Abstract

Enterohemorrhagic Escherichia coli serotype O157:H7 is a pathotype of diarrheagenic E. coli that produces one or more Shiga toxins, forms a characteristic histopathology described as attaching and effacing lesions, and possesses the large virulence plasmid pO157. The bacterium is recognized worldwide, especially in developed countries, as an emerging food-borne bacterial pathogen, which causes disease in humans and in some animals. Healthy cattle are the principal and natural reservoir of E. coli O157:H7, and most disease outbreaks are, therefore, due to consumption of fecally contaminated bovine foods or dairy products. In this review, we provide a general overview of E. coli O157:H7 infection, especially focusing on the bacterial characteristics rather than on the host responses during infection.

Keyword

enterohemorrhagic; Escherichia coli; O157:H7

MeSH Terms

Animals
Cattle
Cattle Diseases/blood/epidemiology
Developing Countries
*Enterohemorrhagic Escherichia coli
Escherichia coli Infections/blood/*epidemiology/veterinary
*Escherichia coli O157/genetics/pathogenicity
Feces/microbiology
Hemolytic-Uremic Syndrome/blood/epidemiology/veterinary
Operon
Shiga Toxins/analysis
Shigella dysenteriae
Virulence

Reference

1. Abbott SL, Hanson DF, Felland TD, Connell S, Shum AH, Janda JM. Escherichia coli O157:H7 generates a unique biochemical profile on MicroScan conventional gram-negative identification panels. J Clin Microbiol. 1994. 32:823–824.

2. Andreoli SP, Trachtman H, Acheson DW, Siegler RL, Obrig TG. Hemolytic uremic syndrome: epidemiology, pathophysiology, and therapy. Pediatr Nephrol. 2002. 17:293–298.

3. Armstrong GD, Fodor E, Vanmaele R. Investigation of Shiga-like toxin binding to chemically synthesized oligosaccharide sequences. J Infect Dis. 1991. 164:1160–1167.

4. Atlung T, Ingmer H. H-NS: a modulator of environmentally regulated gene expression. Mol Microbiol. 1997. 24:7–17.

5. Banatvala N, Griffin PM, Greene KD, Barrett TJ, Bibb WF, Green JH, Wells JG. The United States National Prospective Hemolytic Uremic Syndrome Study: microbiologic, serologic, clinical, and epidemiologic findings. J Infect Dis. 2001. 183:1063–1070.

6. Barker J, Humphrey TJ, Brown MW. Survival of Escherichia coli O157 in a soil protozoan: implications for disease. FEMS Microbiol Lett. 1999. 173:291–295.

7. Belongia EA, Osterholm MT, Soler JT, Ammend DA, Braun JE, MacDonald KL. Transmission of Escherichia coli O157:H7 infection in Minnesota child day-care facilities. JAMA. 1993. 269:883–888.

8. Besser RE, Lett SM, Weber JT, Doyle MP, Barrett TJ, Wells JG, Griffin PM. An outbreak of diarrhea and hemolytic uremic syndrome from Escherichia coli O157:H7 in fresh-pressed apple cider. JAMA. 1993. 269:2217–2220.

9. Bettelheim KA. Commemoration of the publication 100 years ago of the papers by Dr. Th. Escherich in which are described for the first time the organisms that bear his name. Zentralbl Bakteriol Mikrobiol Hyg A. 1986. 261:255–265.

10. Beutin L, Geier D, Zimmermann S, Karch H. Virulence markers of Shiga-like toxin-producing Escherichia coli strains originating from healthy domestic animals of different species. J Clin Microbiol. 1995. 33:631–635.

11. Bilge SS, Vary JC Jr, Dowell SF, Tarr PI. Role of the Escherichia coli O157:H7 O side chain in adherence and analysis of an rfb locus. Infect Immun. 1996. 64:4795–4801.

12. Bonner TI, Brenner DJ, Neufeld BR, Britten RJ. Reduction in the rate of DNA reassociation by sequence divergence. J Mol Biol. 1973. 81:123–135.

13. Brunder W, Schmidt H, Karch H. KatP, a novel catalase-peroxidase encoded by the large plasmid of enterohaemorrhagic Escherichia coli O157:H7. Microbiology. 1996. 142:3305–3315.

14. Brunder W, Schmidt H, Karch H. EspP, a novel extracellular serine protease of enterohaemorrhagic Escherichia coli O157:H7 cleaves human coagulation factor V. Mol Microbiol. 1997. 24:767–778.

15. Buchanan RL, Edelson SG, Boyd G. Effects of pH and acid resistance on the radiation resistance of enterohemorrhagic Escherichia coli. J Food Prot. 1999. 62:219–228.

16. Burland V, Shao Y, Perna NT, Plunkett G, Sofia HJ, Blattner FR. The complete DNA sequence and analysis of the large virulence plasmid of Escherichia coli O157:H7. Nucleic Acids Res. 1998. 26:4196–4204.

17. Buteau C, Proulx F, Chaibou M, Raymond D, Clermont MJ, Mariscalco MM, Lebel MH, Seidman E. Leukocytosis in children with Escherichia coli O157:H7 enteritis developing the hemolytic-uremic syndrome. Pediatr Infect Dis J. 2000. 19:642–647.

18. Buzby JC, Roberts T, Lin C-TJ, MacDonald JM. Agricultural Economic Report No. 741. Bacterial foodborne disease-Medical cost and productivity losses. 1996. Washington DC: Food and Customer Economics Division, Economic Research Service, USDA;21–29.

19. Campellone KG, Leong JM. Tails of two Tirs: actin pedestal formation by enteropathogenic E. coli and enterohemorrhagic E. coli O157:H7. Curr Opin Microbiol. 2003. 6:82–90.

20. Cassels FJ, Wolf MK. Colonization factors of diarrheagenic E. coli and their intestinal receptors. J Ind Microbiol. 1995. 15:214–226.

21. Cherla RP, Lee SY, Tesh VL. Shiga toxins and apoptosis. FEMS Microbiol Lett. 2003. 228:159–166.

22. Cheville AM, Arnold KW, Buchrieser C, Cheng CM, Kaspar CW. rpoS regulation of acid, heat, and salt tolerance in Escherichia coli O157:H7. Appl Environ Microbiol. 1996. 62:1822–1824.

23. Cimolai N, Basalyga S, Mah DG, Morrison BJ, Carter JE. A continuing assessment of risk factors for the development of Escherichia coli O157:H7-associated hemolytic uremic syndrome. Clin Nephrol. 1994. 42:85–89.

24. Cízek A, Literák I, Scheer P. Survival of Escherichia coli O157 in faeces of experimentally infected rats and domestic pigeons. Lett Appl Microbiol. 2000. 31:349–352.

25. Clementz T, Zhou Z, Raetz CR. Function of the Escherichia coli msbB gene, a multicopy suppressor of htrB knockouts, in the acylation of lipid A. Acylation by MsbB follows laurate incorporation by HtrB. J Biol Chem. 1997. 272:10353–10360.

26. Cockerill F 3rd, Beebakhee G, Soni R, Sherman P. Polysaccharide side chains are not required for attaching and effacing adhesion of Escherichia coli O157:H7. Infect Immun. 1996. 64:3196–3200.

27. Cornick NA, Booher SL, Moon HW. Intimin facilitates colonization by Escherichia coli O157:H7 in adult ruminants. Infect Immun. 2002. 70:2704–2707.

28. Degli Esposti M, Dive C. Mitochondrial membrane permeabilisation by Bax/Bak. Biochem Biophys Res Commun. 2003. 304:455–461.

29. DeVinney R, Puente JL, Gauthier A, Goosney D, Finlay BB. Enterohaemorrhagic and enteropathogenic Escherichia coli use a different Tir-based mechanism for pedestal formation. Mol Microbiol. 2001. 41:1445–1458.

30. DeVinney R, Stein M, Reinscheid D, Abe A, Ruschkowski S, Finlay BB. Enterohemorrhagic Escherichia coli O157:H7 produces Tir, which is translocated to the host cell membrane but is not tyrosine phosphorylated. Infect Immun. 1999. 67:2389–2398.

31. Dobrindt U, Agerer F, Michaelis K, Janka A, Buchrieser C, Samuelson M, Svanborg C, Gottschalk G, Karch H, Hacker J. Analysis of genome plasticity in pathogenic and commensal Escherichia coli isolates by use of DNA arrays. J Bacteriol. 2003. 185:1831–1840.

32. Donnenberg MS, Kaper JB. Enteropathogenic Escherichia coli. Infect Immun. 1992. 60:3953–3961.

33. Donnenberg MS, Kaper JB, Finlay BB. Interactions between enteropathogenic Escherichia coli and host epithelial cells. Trends Microbiol. 1997. 5:109–114.

34. Donnenberg MS, Tzipori S, McKee ML, O'Brien AD, Alroy J, Kaper JB. The role of the eae gene of enterohemorrhagic Escherichia coli in intimate attachment in vitro and in a porcine model. J Clin Invest. 1993. 92:1418–1424.

35. Doyle MP, Beuchat LR, Montville TJ. Food Microbiology: Fundamentals and Frontiers. 2001. 2nd ed. Washington DC: ASM Press;171–191.

36. Dulguer MV, Fabbricotti SH, Bando SY, Moreira-Filho CA, Fagundes-Neto U, Scaletsky IC. Atypical enteropathogenic Escherichia coli strains: phenotypic and genetic profiling reveals a strong association between enteroaggregative E. coli heat-stable enterotoxin and diarrhea. J Infect Dis. 2003. 188:1685–1694.

37. Ebel F, Podzadel T, Rohde M, Kresse AU, Krämer S, Deibel C, Guzmán CA, Chakraborty T. Initial binding of Shiga toxin-producing Escherichia coli to host cells and subsequent induction of actin rearrangements depend on filamentous EspA-containing surface appendages. Mol Microbiol. 1998. 30:147–161.

38. Elliott SJ, Yu J, Kaper JB. The cloned locus of enterocyte effacement from enterohemorrhagic Escherichia coli O157:H7 is unable to confer the attaching and effacing phenotype upon E. coli K-12. Infect Immun. 1999. 67:4260–4263.

39. Endo Y. Mechanism of action of ricin and related toxins on the inactivation of eukaryotic ribosomes. Cancer Treat Res. 1988. 37:75–89.

40. Falconi M, Colonna B, Prosseda G, Micheli G, Gualerzi CO. Thermoregulation of Shigella and Escherichia coli EIEC pathogenicity. A temperature-dependent structural transition of DNA modulates accessibility of virF promoter to transcriptional repressor H-NS. EMBO J. 1998. 17:7033–7043.

41. Ferens WA, Cobbold R, Hovde CJ. Intestinal Shiga toxin-producing Escherichia coli bacteria mitigate bovine leukemia virus infection in experimentally infected sheep. Infect Immun. 2006. 74:2906–2916.

42. Ferens WA, Grauke LJ, Hovde CJ. Shiga toxin 1 targets bovine leukemia virus-expressing cells. Infect Immun. 2004. 72:1837–1840.

43. Ferens WA, Halver M, Gustin KE, Ott T, Hovde CJ. Differential sensitivity of viruses to the antiviral activity of Shiga toxin 1 A subunit. Virus Res. 2007. 125:104–108.

44. Ferens WA, Hovde CJ. Antiviral activity of shiga toxin 1: suppression of bovine leukemia virus-related spontaneous lymphocyte proliferation. Infect Immun. 2000. 68:4462–4469.

45. Frankel G, Lider O, Hershkoviz R, Mould AP, Kachalsky SG, Candy DC, Cahalon L, Humphries MJ, Dougan G. The cell-binding domain of intimin from enteropathogenic Escherichia coli binds to beta1 integrins. J Biol Chem. 1996. 271:20359–20364.

46. Frankel G, Phillips AD, Rosenshine I, Dougan G, Kaper JB, Knutton S. Enteropathogenic and enterohaemorrhagic Escherichia coli: more subversive elements. Mol Microbiol. 1998. 30:911–921.

47. Frankel G, Phillips AD, Trabulsi LR, Knutton S, Dougan G, Matthews S. Intimin and the host cell--is it bound to end in Tir(s)? Trends Microbiol. 2001. 9:214–218.

48. Fratamico PM, Bhaduri S, Buchanan RL. Studies on Escherichia coli serotype O157:H7 strains containing a 60-MDa plasmid and on 60-MDa plasmid-cured derivatives. J Med Microbiol. 1993. 39:371–381.

49. Goosney DL, DeVinney R, Finlay BB. Recruitment of cytoskeletal and signaling proteins to enteropathogenic and enterohemorrhagic Escherichia coli pedestals. Infect Immun. 2001. 69:3315–3322.

50. Griffin PM, Tauxe RV. The epidemiology of infections caused by Escherichia coli O157:H7, other enterohemorrhagic E. coli, and the associated hemolytic uremic syndrome. Epidemiol Rev. 1991. 13:60–98.

51. Gruenheid S, DeVinney R, Bladt F, Goosney D, Gelkop S, Gish GD, Pawson T, Finlay BB. Enteropathogenic E. coli Tir binds Nck to initiate actin pedestal formation in host cells. Nat Cell Biol. 2001. 3:856–859.

52. Hancock DD, Besser TE, Kinsel ML, Tarr PI, Rice DH, Paros MG. The prevalence of Escherichia coli O157.H7 in dairy and beef cattle in Washington State. Epidemiol Infect. 1994. 113:199–207.

53. Harris JR, Mariano J, Wells JG, Payne BJ, Donnell HD, Cohen ML. Person-to-person transmission in an outbreak of enteroinvasive Escherichia coli. Am J Epidemiol. 1985. 122:245–252.

54. Heuvelink AE, van Heerwaarden C, Zwartkruis-Nahuis JT, van Oosterom R, Edink K, van Duynhoven YT, de Boer E. Escherichia coli O157 infection associated with a petting zoo. Epidemiol Infect. 2002. 129:295–302.

55. Hildebrand JM, Maguire HC, Holliman RE, Kangesu E. An outbreak of Escherichia coli O157 infection linked to paddling pools. Commun Dis Rep CDR Rev. 1996. 6:R33–R36.

56. Horne C, Vallance BA, Deng W, Finlay BB. Current progress in enteropathogenic and enterohemorrhagic Escherichia coli vaccines. Expert Rev Vaccines. 2002. 1:483–493.

57. Hurley BP, Thorpe CM, Acheson DW. Shiga toxin translocation across intestinal epithelial cells is enhanced by neutrophil transmigration. Infect Immun. 2001. 69:6148–6155.

58. Ide T, Laarmann S, Greune L, Schillers H, Oberleithner H, Schmidt MA. Characterization of translocation pores inserted into plasma membranes by type III-secreted Esp proteins of enteropathogenic Escherichia coli. Cell Microbiol. 2001. 3:669–679.

59. Iizumi Y, Sagara H, Kabe Y, Azuma M, Kume K, Ogawa M, Nagai T, Gillespie PG, Sasakawa C, Handa H. The enteropathogenic E. coli effector EspB facilitates microvillus effacing and antiphagocytosis by inhibiting myosin function. Cell Host Microbe. 2007. 2:383–392.

60. Janka A, Bielaszewska M, Dobrindt U, Karch H. Identification and distribution of the enterohemorrhagic Escherichia coli factor for adherence (efa1) gene in sorbitol-fermenting Escherichia coli O157:H. Int J Med Microbiol. 2002. 292:207–214.

61. Jones NL, Islur A, Haq R, Mascarenhas M, Karmali MA, Perdue MH, Zanke BW, Sherman PM. Escherichia coli Shiga toxins induce apoptosis in epithelial cells that is regulated by the Bcl-2 family. Am J Physiol Gastrointest Liver Physiol. 2000. 278:G811–G819.

62. Junkins AD, Doyle MP. Demonstration of exopolysaccharide production by enterohemorrhagic Escherichia coli. Curr Microbiol. 1992. 25:9–17.

63. Kaniuk NA, Vinogradov E, Li J, Monteiro MA, Whitfield C. Chromosomal and plasmid-encoded enzymes are required for assembly of the R3-type core oligosaccharide in the lipopolysaccharide of Escherichia coli O157:H7. J Biol Chem. 2004. 279:31237–31250.

64. Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia coli. Nat Rev Microbiol. 2004. 2:123–140.

65. Karch H, Heesemann J, Laufs R, O'Brien AD, Tacket CO, Levine MM. A plasmid of enterohemorrhagic Escherichia coli O157:H7 is required for expression of a new fimbrial antigen and for adhesion to epithelial cells. Infect Immun. 1987. 55:455–461.

66. Karmali MA, Steele BT, Petric M, Lim C. Sporadic cases of haemolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia coli in stools. Lancet. 1983. 1:619–620.

67. Kenny B. Phosphorylation of tyrosine 474 of the enteropathogenic Escherichia coli (EPEC) Tir receptor molecule is essential for actin nucleating activity and is preceded by additional host modifications. Mol Microbiol. 1999. 31:1229–1241.

68. Kim SH, Jia W, Bishop RE, Gyles C. An msbB homologue carried in plasmid pO157 encodes an acyltransferase involved in lipid A biosynthesis in Escherichia coli O157:H7. Infect Immun. 2004. 72:1174–1180.

69. Klapproth JM, Scaletsky IC, McNamara BP, Lai LC, Malstrom C, James SP, Donnenberg MS. A large toxin from pathogenic Escherichia coli strains that inhibits lymphocyte activation. Infect Immun. 2000. 68:2148–2155.

70. Knutton S, Rosenshine I, Pallen MJ, Nisan I, Neves BC, Bain C, Wolff C, Dougan G, Frankel G. A novel EspA-associated surface organelle of enteropathogenic Escherichia coli involved in protein translocation into epithelial cells. EMBO J. 1998. 17:2166–2176.

71. Konowalchuk J, Speirs JI, Stavric S. Vero response to a cytotoxin of Escherichia coli. Infect Immun. 1977. 18:775–779.

72. Kudva IT, Blanch K, Hovde CJ. Analysis of Escherichia coli O157:H7 survival in ovine or bovine manure and manure slurry. Appl Environ Microbiol. 1998. 64:3166–3174.

73. Kudva IT, Hatfield PG, Hovde CJ. Escherichia coli O157:H7 in microbial flora of sheep. J Clin Microbiol. 1996. 34:431–433.

74. Lathem WW, Grys TE, Witowski SE, Torres AG, Kaper JB, Tarr PI, Welch RA. StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically cleaves C1 esterase inhibitor. Mol Microbiol. 2002. 45:277–288.

75. Law D. Virulence factors of Escherichia coli O157 and other Shiga toxin-producing E. coli. J Appl Microbiol. 2000. 88:729–745.

76. Leclercq A, Lambert B, Pierard D, Mahillon J. Particular biochemical profiles for enterohemorrhagic Escherichia coli O157:H7 isolates on the ID 32E system. J Clin Microbiol. 2001. 39:1161–1164.

77. LeJeune JT, Besser TE, Hancock DD. Cattle water troughs as reservoirs of Escherichia coli O157. Appl Environ Microbiol. 2001. 67:3053–3057.

78. Levine MM. Escherichia coli that cause diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherent. J Infect Dis. 1987. 155:377–389.

79. Levine MM, Ferreccio C, Prado V, Cayazzo M, Abrego P, Martinez J, Maggi L, Baldini MM, Martin W, Maneval D, Kay B, Guers L, Lior H, Wasserman SS, Nataro JP. Epidemiologic studies of Escherichia coli diarrheal infections in a low socioeconomic level peri-urban community in Santiago, Chile. Am J Epidemiol. 1993. 138:849–869.

80. Levine MM, Xu JG, Kaper JB, Lior H, Prado V, Tall B, Nataro J, Karch H, Wachsmuth K. A DNA probe to identify enterohemorrhagic Escherichia coli of O157:H7 and other serotypes that cause hemorrhagic colitis and hemolytic uremic syndrome. J Infect Dis. 1987. 156:175–182.

81. Lim JY, Sheng H, Seo KS, Park YH, Hovde CJ. Characterization of an Escherichia coli O157:H7 plasmid O157 deletion mutant and its survival and persistence in cattle. Appl Environ Microbiol. 2007. 73:2037–2047.

82. Lin J, Smith MP, Chapin KC, Baik HS, Bennett GN, Foster JW. Mechanisms of acid resistance in enterohemorrhagic Escherichia coli. Appl Environ Microbiol. 1996. 62:3094–3100.

83. Lingwood CA. Role of verotoxin receptors in pathogenesis. Trends Microbiol. 1996. 4:147–153.

84. Louie M, de Azavedo JC, Handelsman MY, Clark CG, Ally B, Dytoc M, Sherman P, Brunton J. Expression and characterization of the eaeA gene product of Escherichia coli serotype O157:H7. Infect Immun. 1993. 61:4085–4092.

85. Mao Y, Doyle MP, Chen J. Insertion mutagenesis of wca reduces acid and heat tolerance of enterohemorrhagic Escherichia coli O157:H7. J Bacteriol. 2001. 183:3811–3815.

86. March SB, Ratnam S. Sorbitol-MacConkey medium for detection of Escherichia coli O157:H7 associated with hemorrhagic colitis. J Clin Microbiol. 1986. 23:869–872.

87. McKee ML, O'Brien AD. Investigation of enterohemorrhagic Escherichia coli O157:H7 adherence characteristics and invasion potential reveals a new attachment pattern shared by intestinal E. coli. Infect Immun. 1995. 63:2070–2074.

88. Mead PS, Slutsker L, Dietz V, McCaig LF, Bresee JS, Shapiro C, Griffin PM, Tauxe RV. Food-related illness and death in the United States. Emerg Infect Dis. 1999. 5:607–625.

89. Mellies JL, Barron AM, Carmona AM. Enteropathogenic and enterohemorrhagic Escherichia coli virulence gene regulation. Infect Immun. 2007. 75:4199–4210.

90. Melton-Celsa AR, O'Brien AD. O'Brien AD, Kaper JB, editors. Structure, biology, and relative toxicity of Shiga toxin family members for cells and animals. Escherichia coli O157:H7 and other Shiga-toxin-producing E. coli strains. 1998. Washington DC: American Society for Microbiology;121–128.

91. Mora A, Blanco M, Blanco JE, Dahbi G, López C, Justel P, Alonso MP, Echeita A, Bernárdez MI, González EA, Blanco J. Serotypes, virulence genes and intimin types of Shiga toxin (verocytotoxin)-producing Escherichia coli isolates from minced beef in Lugo (Spain) from 1995 through 2003. BMC Microbiol. 2007. 7:13.

92. Nataro JP, Deng Y, Maneval DR, German AL, Martin WC, Levine MM. Aggregative adherence fimbriae I of enteroaggregative Escherichia coli mediate adherence to HEp-2 cells and hemagglutination of human erythrocytes. Infect Immun. 1992. 60:2297–2304.

93. Nataro JP, Kaper JB. Diarrheagenic Escherichia coli. Clin Microbiol Rev. 1998. 11:142–201.

94. Nataro JP, Kaper JB, Robins-Browne R, Prado V, Vial P, Levine MM. Patterns of adherence of diarrheagenic Escherichia coli to HEp-2 cells. Pediatr Infect Dis J. 1987. 6:829–831.

95. O'Brien AD, Tesh VL, Donohue-Rolfe A, Jackson MP, Olsnes S, Sandvig K, Lindberg AA, Keusch GT. Shiga toxin: biochemistry, genetics, mode of action, and role in pathogenesis. Curr Top Microbiol Immunol. 1992. 180:65–94.

96. O'Loughlin EV, Robins-Browne RM. Effect of Shiga toxin and Shiga-like toxins on eukaryotic cells. Microbes Infect. 2001. 3:493–507.

97. Ohyama T. Intrinsic DNA bends: an organizer of local chromatin structure for transcription. Bioessays. 2001. 23:708–715.

98. Ostroff SM, Tarr PI, Neill MA, Lewis JH, Hargrett-Bean N, Kobayashi JM. Toxin genotypes and plasmid profiles as determinants of systemic sequelae in Escherichia coli O157:H7 infections. J Infect Dis. 1989. 160:994–998.

99. Paton AW, Voss E, Manning PA, Paton JC. Antibodies to lipopolysaccharide block adherence of Shiga toxin-producing Escherichia coli to human intestinal epithelial (Henle 407) cells. Microb Pathog. 1998. 24:57–63.

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

101. Pérez-Martín J, Espinosa M. Correlation between DNA bending and transcriptional activation at a plasmid promoter. J Mol Biol. 1994. 241:7–17.

102. Pérez-Martín J, Rojo F, de Lorenzo V. Promoters responsive to DNA bending: a common theme in prokaryotic gene expression. Microbiol Rev. 1994. 58:268–290.

103. Perna NT, Mayhew GF, Pósfai G, Elliott S, Donnenberg MS, Kaper JB, Blattner FR. Molecular evolution of a pathogenicity island from enterohemorrhagic Escherichia coli O157:H7. Infect Immun. 1998. 66:3810–3817.

104. Perna NT, Plunkett G 3rd, 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. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature. 2001. 409:529–533.

105. Price SB, Cheng CM, Kaspar CW, Wright JC, DeGraves FJ, Penfound TA, Castanie-Cornet MP, Foster JW. Role of rpoS in acid resistance and fecal shedding of Escherichia coli O157:H7. Appl Environ Microbiol. 2000. 66:632–637.

106. Raetz CR, Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem. 2002. 71:635–700.

107. Ratnam S, March SB, Ahmed R, Bezanson GS, Kasatiya S. Characterization of Escherichia coli serotype O157:H7. J Clin Microbiol. 1988. 26:2006–2012.

108. Rice DH, Hancock DD, Besser TE. Verotoxigenic E. coli O157 colonisation of wild deer and range cattle. Vet Rec. 1995. 137:524.

109. Riley LW, Remis RS, Helgerson SD, McGee HB, Wells JG, Davis BR, Hebert RJ, Olcott ES, Johnson LM, Hargrett NT, Blake PA, Cohen ML. Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med. 1983. 308:681–685.

110. Roe AJ, Hoey DE, Gally DL. Regulation, secretion and activity of type III-secreted proteins of enterohaemorrhagic Escherichia coli O157. Biochem Soc Trans. 2003. 31:98–103.

111. Rohatgi R, Nollau P, Ho HY, Kirschner MW, Mayer BJ. Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway. J Biol Chem. 2001. 276:26448–26452.

112. Rowbury RJ. An assessment of environmental factors influencing acid tolerance and sensitivity in Escherichia coli, Salmonella spp. and other enterobacteria. Lett Appl Microbiol. 1995. 20:333–337.

113. Sandvig K, van Deurs B. Transport of protein toxins into cells: pathways used by ricin, cholera toxin and Shiga toxin. FEBS Lett. 2002. 529:49–53.

114. Scaletsky IC, Silva ML, Trabulsi LR. Distinctive patterns of adherence of enteropathogenic Escherichia coli to HeLa cells. Infect Immun. 1984. 45:534–536.

115. Schmidt H, Geitz C, Tarr PI, Frosch M, Karch H. Non-O157:H7 pathogenic Shiga toxin-producing Escherichia coli: phenotypic and genetic profiling of virulence traits and evidence for clonality. J Infect Dis. 1999. 179:115–123.

116. Schmidt H, Henkel B, Karch H. A gene cluster closely related to type II secretion pathway operons of gram-negative bacteria is located on the large plasmid of enterohemorrhagic Escherichia coli O157 strains. FEMS Microbiol Lett. 1997. 148:265–272.

117. Schmidt H, Karch H, Beutin L. The large-sized plasmids of enterohemorrhagic Escherichia coli O157 strains encode hemolysins which are presumably members of the E. coli alpha-hemolysin family. FEMS Microbiol Lett. 1994. 117:189–196.

118. Scotland SM, Willshaw GA, Smith HR, Rowe B. Properties of strains of Escherichia coli O26:H11 in relation to their enteropathogenic or enterohemorrhagic classification. J Infect Dis. 1990. 162:1069–1074.

119. Sears CL, Kaper JB. Enteric bacterial toxins: mechanisms of action and linkage to intestinal secretion. Microbiol Rev. 1996. 60:167–215.

120. Sheng H, Lim JY, Watkins MK, Minnich SA, Hovde CJ. Characterization of an Escherichia coli O157:H7 O-antigen deletion mutant and effect of the deletion on bacterial persistence in the mouse intestine and colonization at the bovine terminal rectal mucosa. Appl Environ Microbiol. 2008. 74:5015–5022.

121. Sherman P, Cockerill F 3rd, Soni R, Brunton J. Outer membranes are competitive inhibitors of Escherichia coli O157:H7 adherence to epithelial cells. Infect Immun. 1991. 59:890–899.

122. Sherman PM, Soni R. Adherence of Vero cytotoxin-producing Escherichia coli of serotype O157:H7 to human epithelial cells in tissue culture: role of outer membranes as bacterial adhesins. J Med Microbiol. 1988. 26:11–17.

123. Siegler RL, Pysher TJ, Lou R, Tesh VL, Taylor FB Jr. Response to Shiga toxin-1, with and without lipopolysaccharide, in a primate model of hemolytic uremic syndrome. Am J Nephrol. 2001. 21:420–425.

124. Sinclair JF, O'Brien AD. Cell surface-localized nucleolin is a eukaryotic receptor for the adhesin intimin-gamma of enterohemorrhagic Escherichia coli O157:H7. J Biol Chem. 2002. 277:2876–2885.

125. Slutsker L, Ries AA, Greene KD, Wells JG, Hutwagner L, Griffin PM. Escherichia coli O157:H7 diarrhea in the United States: clinical and epidemiologic features. Ann Intern Med. 1997. 126:505–513.

126. Small PL, Falkow S. Identification of regions on a 230-kilobase plasmid from enteroinvasive Escherichia coli that are required for entry into HEp-2 cells. Infect Immun. 1988. 56:225–229.

127. Smith AE, Kim SH, Liu F, Jia W, Vinogradov E, Gyles CL, Bishop RE. PagP activation in the outer membrane triggers R3 core oligosaccharide truncation in the cytoplasm of Escherichia coli O157:H7. J Biol Chem. 2008. 283:4332–4343.

128. Smith HR, Scotland SM. ACP Broadsheet 135: January 1993. Isolation and identification methods for Escherichia coli O157 and other Vero cytotoxin producing strains. J Clin Pathol. 1993. 46:10–17.

129. Somerville JE Jr, Cassiano L, Bainbridge B, Cunningham MD, Darveau RP. A novel Escherichia coli lipid A mutant that produces an antiinflammatory lipopolysaccharide. J Clin Invest. 1996. 97:359–365.

130. Spika JS, Parsons JE, Nordenberg D, Wells JG, Gunn RA, Blake PA. Hemolytic uremic syndrome and diarrhea associated with Escherichia coli O157:H7 in a day care center. J Pediatr. 1986. 109:287–291.

131. Tarr PI, Bilge SS, Vary JC Jr, Jelacic S, Habeeb RL, Ward TR, Baylor MR, Besser TE. Iha: a novel Escherichia coli O157:H7 adherence-conferring molecule encoded on a recently acquired chromosomal island of conserved structure. Infect Immun. 2000. 68:1400–1407.

132. Tatsuno I, Horie M, Abe H, Miki T, Makino K, Shinagawa H, Taguchi H, Kamiya S, Hayashi T, Sasakawa C. toxB gene on pO157 of enterohemorrhagic Escherichia coli O157:H7 is required for full epithelial cell adherence phenotype. Infect Immun. 2001. 69:6660–6669.

133. Thompson JS, Hodge DS, Borczyk AA. Rapid biochemical test to identify verocytotoxin-positive strains of Escherichia coli serotype O157. J Clin Microbiol. 1990. 28:2165–2168.

134. Thorpe CM. Shiga toxin-producing Escherichia coli infection. Clin Infect Dis. 2004. 38:1298–1303.

135. Tobe T, Beatson SA, Taniguchi H, Abe H, Bailey CM, Fivian A, Younis R, Matthews S, Marches O, Frankel G, Hayashi T, Pallen MJ. 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. 2006. 103:14941–14946.

136. Torres AG, Kaper JB. Multiple elements controlling adherence of enterohemorrhagic Escherichia coli O157:H7 to HeLa cells. Infect Immun. 2003. 71:4985–4995.

137. Tulloch EF Jr, Ryan KJ, Formal SB, Franklin FA. Invasive enteropathic Escherichia coli dysentery. An outbreak in 28 adults. Ann Intern Med. 1973. 79:13–17.

138. Tzipori S, Gunzer F, Donnenberg MS, de Montigny L, Kaper JB, Donohue-Rolfe A. The role of the eaeA gene in diarrhea and neurological complications in a gnotobiotic piglet model of enterohemorrhagic Escherichia coli infection. Infect Immun. 1995. 63:3621–3627.

139. Tzipori S, Karch H, Wachsmuth KI, Robins-Browne RM, O'Brien AD, Lior H, Cohen ML, Smithers J, Levine MM. Role of a 60-megadalton plasmid and Shiga-like toxins in the pathogenesis of infection caused by enterohemorrhagic Escherichia coli O157:H7 in gnotobiotic piglets. Infect Immun. 1987. 55:3117–3125.

140. Varma JK, Greene KD, Reller ME, DeLong SM, Trottier J, Nowicki SF, DiOrio M, Koch EM, Bannerman TL, York ST, Lambert-Fair MA, Wells JG, Mead PS. An outbreak of Escherichia coli O157 infection following exposure to a contaminated building. JAMA. 2003. 290:2709–2712.

141. Vorachek-Warren MK, Ramirez S, Cotter RJ, Raetz CR. A triple mutant of Escherichia coli lacking secondary acyl chains on lipid A. J Biol Chem. 2002. 277:14194–14205.

142. Waddell TE, Lingwood CA, Gyles CL. Interaction of verotoxin 2e with pig intestine. Infect Immun. 1996. 64:1714–1719.

143. Wadolkowski EA, Burris JA, O'Brien AD. Mouse model for colonization and disease caused by enterohemorrhagic Escherichia coli O157:H7. Infect Immun. 1990. 58:2438–2445.

144. Wallace JS, Cheasty T, Jones K. Isolation of vero cytotoxin-producing Escherichia coli O157 from wild birds. J Appl Microbiol. 1997. 82:399–404.

145. Wang G, Doyle MP. Survival of enterohemorrhagic Escherichia coli O157:H7 in water. J Food Prot. 1998. 61:662–667.

146. Wells JG, Davis BR, Wachsmuth IK, Riley LW, Remis RS, Sokolow R, Morris GK. Laboratory investigation of hemorrhagic colitis outbreaks associated with a rare Escherichia coli serotype. J Clin Microbiol. 1983. 18:512–520.

147. Whittam TS. Kaper JB, O'Brien AD, editors. Evolution of Escherichia coli O157:H7 and other Shiga toxin-producing E. coli strains. Escherichia coli O157:H7 and Other Shiga Toxin-Producing E. coli Strains. 1998. Washington DC: American Society for Microbiology;195–209.

148. Whittam TS, Wachsmuth IK, Wilson RA. Genetic evidence of clonal descent of Escherichia coli O157:H7 associated with hemorrhagic colitis and hemolytic uremic syndrome. J Infect Dis. 1988. 157:1124–1133.

149. Whittam TS, Wilson RA. Genetic relationships among pathogenic strains of avian Escherichia coli. Infect Immun. 1988. 56:2458–2466.

150. Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med. 2000. 342:1930–1936.

151. Yoon JW, Lim JY, Park YH, Hovde CJ. Involvement of the Escherichia coli O157:H7(pO157) ecf operon and lipid A myristoyl transferase activity in bacterial survival in the bovine gastrointestinal tract and bacterial persistence in farm water troughs. Infect Immun. 2005. 73:2367–2378.

152. Yoon JW, Minnich SA, Ahn JS, Park YH, Paszczynski A, Hovde CJ. Thermoregulation of the Escherichia coli O157:H7 pO157 ecf operon and lipid A myristoyl transferase activity involves intrinsically curved DNA. Mol Microbiol. 2004. 51:419–435.

153. Yu J, Kaper JB. Cloning and characterization of the eae gene of enterohaemorrhagic Escherichia coli O157:H7. Mol Microbiol. 1992. 6:411–417.

154. Yuk HG, Marshall DL. Heat adaptation alters Escherichia coli O157:H7 membrane lipid composition and verotoxin production. Appl Environ Microbiol. 2003. 69:5115–5119.