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O104:H4 Pathogenesis: an Enteroaggregative /Shiga Toxin-Producing Explosive Cocktail of High Virulence

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  • Author: Fernando Navarro-Garcia1
  • Editors: Vanessa Sperandio2, Carolyn J. Hovde3
    Affiliations: 1: Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del IPN, México DF, Mexico; 2: University of Texas Southwestern Medical Center, Dallas, TX; 3: University of Idaho, Moscow, ID
  • Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.EHEC-0008-2013
  • Received 08 May 2013 Accepted 29 July 2013 Published 14 November 2014
  • Fernando Navarro-Garcia, [email protected]
image of <span class="jp-italic">Escherichia coli</span> O104:H4 Pathogenesis: an Enteroaggregative <span class="jp-italic">E. coli</span>/Shiga Toxin-Producing <span class="jp-italic">E. coli</span> Explosive Cocktail of High Virulence
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  • Abstract:

    A major outbreak caused by of serotype O104:H4 spread throughout Europe in 2011. This large outbreak was caused by an unusual strain that is most similar to enteroaggregative (EAEC) of serotype O104:H4. A significant difference, however, is the presence of a prophage encoding the Shiga toxin, which is characteristic of enterohemorrhagic (EHEC) strains. This combination of genomic features, associating characteristics from both EAEC and EHEC, represents a new pathotype. The 2011 O104:H4 outbreak of hemorrhagic diarrhea in Germany is an example of the explosive cocktail of high virulence and resistance that can emerge in this species. A total of 46 deaths, 782 cases of hemolytic-uremic syndrome, and 3,128 cases of acute gastroenteritis were attributed to this new clone of EAEC/EHEC. In addition, recent identification in France of similar O104:H4 clones exhibiting the same virulence factors suggests that the EHEC O104:H4 pathogen has become endemically established in Europe after the end of the outbreak. EAEC strains of serotype O104:H4 contain a large set of virulence-associated genes regulated by the AggR transcription factor. They include, among other factors, the pAA plasmid genes encoding the aggregative adherence fimbriae, which anchor the bacterium to the intestinal mucosa (stacked-brick adherence pattern on epithelial cells). Furthermore, sequencing studies showed that horizontal genetic exchange allowed for the emergence of the highly virulent Shiga toxin-producing EAEC O104:H4 strain that caused the German outbreak. This article discusses the role these virulence factors could have in EAEC/EHEC O104:H4 pathogenesis.

  • Citation: Navarro-Garcia F. 2014. O104:H4 Pathogenesis: an Enteroaggregative /Shiga Toxin-Producing Explosive Cocktail of High Virulence. Microbiol Spectrum 2(6):EHEC-0008-2013. doi:10.1128/microbiolspec.EHEC-0008-2013.


1. Frank C, Werber D, Cramer JP, Askar M, Faber M, an der Heiden M, Bernard H, Fruth A, Prager R, Spode A, Wadl M, Zoufaly A, Jordan S, Kemper MJ, Follin P, Muller L, King LA, Rosner B, Buchholz U, Stark K, Krause G. 2011. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med 365:1771–1780. [PubMed][CrossRef]
2. Gault G, Weill FX, Mariani-Kurkdjian P, Jourdan-da Silva N, King L, Aldabe B, Charron M, Ong N, Castor C, Mace M, Bingen E, Noel H, Vaillant V, Bone A, Vendrely B, Delmas Y, Combe C, Bercion R, d'Andigne E, Desjardin M, de Valk H, Rolland P. 2011. Outbreak of haemolytic uraemic syndrome and bloody diarrhoea due to Escherichia coli O104:H4, south-west France, June 2011. Euro Surveill 16.
3. Bielaszewska M, Mellmann A, Zhang W, Kock R, Fruth A, Bauwens A, Peters G, Karch H. 2011. Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. Lancet Infect Dis 11:671–676. [CrossRef]
4. Mellmann A, Harmsen D, Cummings CA, Zentz EB, Leopold SR, Rico A, Prior K, Szczepanowski R, Ji Y, Zhang W, McLaughlin SF, Henkhaus JK, Leopold B, Bielaszewska M, Prager R, Brzoska PM, Moore RL, Guenther S, Rothberg JM, Karch H. 2011. Prospective genomic characterization of the German enterohemorrhagic Escherichia coli O104:H4 outbreak by rapid next generation sequencing technology. PLoS One 6:e22751. [PubMed][CrossRef]
5. Rasko DA, Webster DR, Sahl JW, Bashir A, Boisen N, Scheutz F, Paxinos EE, Sebra R, Chin CS, Iliopoulos D, Klammer A, Peluso P, Lee L, Kislyuk AO, Bullard J, Kasarskis A, Wang S, Eid J, Rank D, Redman JC, Steyert SR, Frimodt-Moller J, Struve C, Petersen AM, Krogfelt KA, Nataro JP, Schadt EE, Waldor MK. 2011. Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany. N Engl J Med 365:709–717. [PubMed][CrossRef]
6. Wieler LH, Semmler T, Eichhorn I, Antao EM, Kinnemann B, Geue L, Karch H, Guenther S, Bethe A. 2011. No evidence of the Shiga toxin-producing E. coli O104:H4 outbreak strain or enteroaggregative E. coli (EAEC) found in cattle faeces in northern Germany, the hotspot of the 2011 HUS outbreak area. Gut Pathog 3:17. [PubMed][CrossRef]
7. Auvray F, Dilasser F, Bibbal D, Kerouredan M, Oswald E, Brugere H. 2012. French cattle is not a reservoir of the highly virulent enteroaggregative Shiga toxin-producing Escherichia coli of serotype O104:H4. Vet Microbiol 158:443–445. [PubMed][CrossRef]
8. Monecke S, Mariani-Kurkdjian P, Bingen E, Weill FX, Baliere C, Slickers P, Ehricht R. 2011. Presence of enterohemorrhagic Escherichia coli ST678/O104:H4 in France prior to 2011. Appl Environ Microbiol 77:8784–8786. [PubMed][CrossRef]
9. Huang DB, Mohanty A, DuPont HL, Okhuysen PC, Chiang T. 2006. A review of an emerging enteric pathogen: enteroaggregative Escherichia coli. J Med Microbiol 55:1303–1311. [PubMed][CrossRef]
10. Nataro JP, Yikang D, Yingkang D, Walker K. 1994. AggR, a transcriptional activator of aggregative adherence fimbria I expression in enteroaggregative Escherichia coli. J Bacteriol 176:4691–4699. [PubMed]
11. Elias WP, Jr, Czeczulin JR, Henderson IR, Trabulsi LR, Nataro JP. 1999. Organization of biogenesis genes for aggregative adherence fimbria II defines a virulence gene cluster in enteroaggregative Escherichia coli. J Bacteriol 181:1779–1785. [PubMed]
12. Bernier C, Gounon P, Le Bouguenec C. 2002. Identification of an aggregative adhesion fimbria (AAF) type III-encoding operon in enteroaggregative Escherichia coli as a sensitive probe for detecting the AAF-encoding operon family. Infect Immun 70:4302–4311. [PubMed][CrossRef]
13. Servin AL. 2005. Pathogenesis of Afa/Dr diffusely adhering Escherichia coli. Clin Microbiol Rev 18:264–292. [PubMed][CrossRef]
14. Boisen N, Struve C, Scheutz F, Krogfelt KA, Nataro JP. 2008. New adhesin of enteroaggregative Escherichia coli related to the Afa/Dr/AAF family. Infect Immun 76:3281–3292. [PubMed][CrossRef]
15. Nataro JP, Deng Y, Maneval DR, German AL, Martin WC, Levine MM. 1992. Aggregative adherence fimbriae I of enteroaggregative Escherichia coli mediate adherence to HEp-2 cells and hemagglutination of human erythrocytes. InfectImmun 60:2297–2304. [PubMed]
16. Savarino SJ, Fox P, Deng Y, Nataro JP. 1994. Identification and characterization of a gene cluster mediating enteroaggregative Escherichia coli aggregative adherence fimbria I biogenesis. J Bacteriol 176:4949–4957. [PubMed]
17. Behrens M, Sheikh J, Nataro JP. 2002. Regulation of the overlapping pic/set locus in Shigella flexneri and enteroaggregative Escherichia coli. Infect Immun 70:2915–2925. [PubMed][CrossRef]
18. Fasano A, Noriega FR, Liao FM, Wang W, Levine MM. 1997. Effect of shigella enterotoxin 1 (ShET1) on rabbit intestine in vitro and in vivo. Gut 40:505–511. [PubMed][CrossRef]
19. Gutierrez-Jimenez J, Arciniega I, Navarro-Garcia F. 2008. The serine protease motif of Pic mediates a dose-dependent mucolytic activity after binding to sugar constituents of the mucin substrate. Microb Pathog 45:115–123. [PubMed][CrossRef]
20. Navarro-Garcia F, Gutierrez-Jimenez J, Garcia-Tovar C, Castro LA, Salazar-Gonzalez H, Cordova V. 2010. Pic, an autotransporter protein secreted by different pathogens in the Enterobacteriaceae family, is a potent mucus secretagogue. Infect Immun 78:4101–4109. [PubMed][CrossRef]
21. Al-Hasani K, Navarro-Garcia F, Huerta J, Sakellaris H, Adler B. 2009. The immunogenic SigA enterotoxin of Shigella flexneri 2a binds to HEp-2 cells and induces fodrin redistribution in intoxicated epithelial cells. PLoS One 4:e8223. [PubMed][CrossRef]
22. Benjelloun-Touimi Z, Sansonetti PJ, Parsot C. 1995. SepA, the major extracellular protein of Shigella flexneri: autonomous secretion and involvement in tissue invasion. Mol Microbiol 17:123–135. [PubMed][CrossRef]
23. Paton AW, Paton JC. 1998. Detection and characterization of Shiga toxigenic Escherichia coli by using multiplex PCR assays for stx1, stx2, eaeA, enterohemorrhagic E. coli hlyA, rfbO111, and rfbO157. J Clin Microbiol 36:598–602. [PubMed]
24. Scheutz F, Teel LD, Beutin L, Pierard D, Buvens G, Karch H, Mellmann A, Caprioli A, Tozzoli R, Morabito S, Strockbine NA, Melton-Celsa AR, Sanchez M, Persson S, O'Brien AD. 2005. Multicenter evaluation of a sequence-based protocol for subtyping Shiga toxins and standardizing Stx nomenclature. J Clin Microbiol 50:2951–263. [PubMed][CrossRef]
25. 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. [PubMed][CrossRef]
26. 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 43:1160–1167. [PubMed][CrossRef]
27. Mey AR, Wyckoff EE, Oglesby AG, Rab E, Taylor RK, Payne SM. 2002. Identification of the Vibrio cholerae enterobactin receptors VctA and IrgA: IrgA is not required for virulence. Infect Immun 70:3419–3426. [PubMed][CrossRef]
28. 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 68:1400–1407. [PubMed][CrossRef]
29. Leveille S, Caza M, Johnson JR, Clabots C, Sabri M, Dozois CM. 2006. Iha from an Escherichia coli urinary tract infection outbreak clonal group A strain is expressed in vivo in the mouse urinary tract and functions as a catecholate siderophore receptor. Infect Immun 74:3427–3436. [PubMed][CrossRef]
30. Pierard D, De Greve H, Haesebrouck F, Mainil J. 2012. O157:H7 and O104:H4 Vero/Shiga toxin-producing Escherichia coli outbreaks: respective role of cattle and humans. Vet Res 43:13. [PubMed][CrossRef]
31. Gyles CL. 2007. Shiga toxin-producing Escherichia coli: an overview. J Anim Sci 85:E45–E62. [PubMed][CrossRef]
32. 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. [PubMed][CrossRef]
33. Kaper JB, Nataro JP, Mobley HL. 2004. Pathogenic Escherichia coli. Nat Rev Microbiol 2:123–140. [PubMed][CrossRef]
34. Knutton S, Lloyd DR, McNeish AS. 1987. Adhesion of enteropathogenic Escherichia coli to human intestinal enterocytes and cultured human intestinal mucosa. Infect Immun 55:69–77. [PubMed]
35. Elliott SJ, Wainwright LA, McDaniel TK, Jarvis KG, Deng YK, Lai LC, McNamara BP, Donnenberg MS, Kaper JB. 1998. The complete sequence of the locus of enterocyte effacement (LEE) from enteropathogenic Escherichia coli E2348/69. Mol Microbiol 28:1–4. [PubMed][CrossRef]
36. Elliott SJ, Sperandio V, Giron JA, Shin S, Mellies JL, Wainwright L, Hutcheson SW, McDaniel TK, Kaper JB. 2000. The locus of enterocyte effacement (LEE)-encoded regulator controls expression of both LEE- and non-LEE-encoded virulence factors in enteropathogenic and enterohemorrhagic Escherichia coli. Infect Immun 68:6115–6126. [PubMed][CrossRef]
37. Deng W, Li Y, Hardwidge PR, Frey EA, Pfuetzner RA, Lee S, Gruenheid S, Strynakda NC, Puente JL, Finlay BB. 2005. Regulation of type III secretion hierarchy of translocators and effectors in attaching and effacing bacterial pathogens. Infect Immun 73:2135–2146. [PubMed][CrossRef]
38. 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 87:7839–7843. [PubMed][CrossRef]
39. Abe A, de Grado M, Pfuetzner RA, Sanchez-Sanmartin C, Devinney R, Puente JL, Strynadka NC, Finlay BB. 1999. Enteropathogenic Escherichia coli translocated intimin receptor, Tir, requires a specific chaperone for stable secretion. Mol Microbiol 33:1162–1175. [PubMed][CrossRef]
40. Elliott SJ, Hutcheson SW, Dubois MS, Mellies JL, Wainwright LA, Batchelor M, Frankel G, Knutton S, Kaper JB. 1999. Identification of CesT, a chaperone for the type III secretion of Tir in enteropathogenic Escherichia coli. Mol Microbiol 33:1176–1189. [PubMed][CrossRef]
41. 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 91:511–520. [PubMed][CrossRef]
42. Navarro-Garcia F, Serapio-Palacios A, Ugalde-Silva P, Tapia-Pastrana G, Chavez-Duenas L. 2013. Actin cytoskeleton manipulation by effector proteins secreted by diarrheagenic Escherichia coli pathotypes. Biomed Res Int 2013:374395. [PubMed][CrossRef]
43. Karmali MA. 2003. The medical significance of Shiga toxin-producing Escherichia coli infections. An overview. Methods Mol Med 73:1–7. [PubMed]
44. Gal-Mor O, Finlay BB. 2006. Pathogenicity islands: a molecular toolbox for bacterial virulence. Cell Microbiol 8:1707–1719. [PubMed][CrossRef]
45. Coombes BK, Gilmour MW, Goodman CD. 2011. The evolution of virulence in non-O157 Shiga toxin-producing Escherichia coli. Front Microbiol 2:90. [PubMed][CrossRef]
46. Ju W, Shen J, Toro M, Zhao S, Meng J. 2013. Distribution of pathogenicity islands OI-122, OI-43/48, OI-57 and a high-pathogenicity island (in Shiga toxin-producing Escherichia coli. Appl Environ Microbiol 79:3406–3412. [PubMed][CrossRef]
47. Schmidt H, Zhang WL, Hemmrich U, Jelacic S, Brunder W, Tarr PI, Dobrindt U, Hacker J, Karch H. 2001. Identification and characterization of a novel genomic island integrated at sel C in locus of enterocyte effacement-negative, Shiga toxin-producing Escherichia coli. Infect Immun 69:6863–6873. [PubMed][CrossRef]
48. Newton HJ, Sloan J, Bulach DM, Seemann T, Allison CC, Tauschek M, Robins-Browne RM, Paton JC, Whittam TS, Paton AW, Hartland EL. 2009. Shiga toxin-producing Escherichia coli strains negative for locus of enterocyte effacement. Emerg Infect Dis 15:372–380. [PubMed][CrossRef]
49. Xu X, McAteer SP, Tree JJ, Shaw DJ, Wolfson EB, Beatson SA, Roe AJ, Allison LJ, Chase-Topping ME, Mahajan A, Tozzoli R, Woolhouse ME, Morabito S, Gally DL. 2012. Lysogeny with Shiga toxin 2-encoding bacteriophages represses type III secretion in enterohemorrhagic Escherichia coli. PLoS Pathog 8:e1002672. [PubMed][CrossRef]
50. Imamovic L, Jofre J, Schmidt H, Serra-Moreno R, Muniesa M. 2009. Phage-mediated Shiga toxin 2 gene transfer in food and water. Appl Environ Microbiol 75:1764–1768. [PubMed][CrossRef]
51. Strockbine NA, Jackson MP, Sung LM, Holmes RK, O'Brien AD. 1988. Cloning and sequencing of the genes for Shiga toxin from Shigella dysenteriae type 1. J Bacteriol 170:1116–1122. [PubMed]
52. Tesh VL. Induction of apoptosis by Shiga toxins. Future Microbiol 5:431–453. [PubMed][CrossRef]
53. Tam P, Mahfoud R, Nutikka A, Khine AA, Binnington B, Paroutis P, Lingwood C. 2008. Differential intracellular transport and binding of verotoxin 1 and verotoxin 2 to globotriaosylceramide-containing lipid assemblies. J Cell Physiol 216:750–763. [PubMed][CrossRef]
54. Chark D, Nutikka A, Trusevych N, Kuzmina J, Lingwood C. 2004. Differential carbohydrate epitope recognition of globotriaosyl ceramide by verotoxins and a monoclonal antibody. Eur J Biochem 271:405–417. [PubMed][CrossRef]
55. 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. [PubMed][CrossRef]
56. Lingwood CA. 1996. Role of verotoxin receptors in pathogenesis. Trends Microbiol 4:147–153. [PubMed][CrossRef]
57. Okuda T, Tokuda N, Numata S, Ito M, Ohta M, Kawamura K, Wiels J, Urano T, Tajima O, Furukawa K. 2006. Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins. J Biol Chem 281:10230–10235. [PubMed][CrossRef]
58. Bast DJ, Banerjee L, Clark C, Read RJ, Brunton JL. 1999. The identification of three biologically relevant globotriaosyl ceramide receptor binding sites on the Verotoxin 1 B subunit. Mol Microbiol 32:953–960. [PubMed][CrossRef]
59. Schweppe CH, Bielaszewska M, Pohlentz G, Friedrich AW, Buntemeyer H, Schmidt MA, Kim KS, Peter-Katalinic J, Karch H, Muthing J. 2008. Glycosphingolipids in vascular endothelial cells: relationship of heterogeneity in Gb3Cer/CD77 receptor expression with differential Shiga toxin 1 cytotoxicity. Glycoconj J 25:291–304. [PubMed][CrossRef]
60. Romer W, Berland L, Chambon V, Gaus K, Windschiegl B, Tenza D, Aly MR, Fraisier V, Florent JC, Perrais D, Lamaze C, Raposo G, Steinem C, Sens P, Bassereau P, Johannes L. 2007. Shiga toxin induces tubular membrane invaginations for its uptake into cells. Nature 450:670–675. [PubMed][CrossRef]
61. Falguieres T, Mallard F, Baron C, Hanau D, Lingwood C, Goud B, Salamero J, Johannes L. 2001. Targeting of Shiga toxin B-subunit to retrograde transport route in association with detergent-resistant membranes. Mol Biol Cell 12:2453–2468. [PubMed][CrossRef]
62. Spilsberg B, Llorente A, Sandvig K. 2007. Polyunsaturated fatty acids regulate Shiga toxin transport. Biochem Biophys Res Commun 364:283–288. [PubMed][CrossRef]
63. Mahfoud R, Manis A, Binnington B, Ackerley C, Lingwood CA. 2010. A major fraction of glycosphingolipids in model and cellular cholesterol-containing membranes is undetectable by their binding proteins. J Biol Chem 285:36049–36059. [PubMed][CrossRef]
64. Lingwood CA, Binnington B, Manis A, Branch DR. 2010. Globotriaosyl ceramide receptor function – where membrane structure and pathology intersect. FEBS Lett 584:1879–1886. [PubMed][CrossRef]
65. Boyd B, Lingwood C. 1989. Verotoxin receptor glycolipid in human renal tissue. Nephron 51:207–210. [PubMed][CrossRef]
66. Lingwood CA. 1994. Verotoxin-binding in human renal sections. Nephron 66:21–28. [PubMed][CrossRef]
67. Pudymaitis A, Armstrong G, Lingwood CA. 1991. Verotoxin-resistant cell clones are deficient in the glycolipid globotriosylceramide: differential basis of phenotype. Arch Biochem Biophys 286:448–452. [PubMed][CrossRef]
68. 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. [PubMed][CrossRef]
69. Sandvig K, Bergan J, Dyve AB, Skotland T, Torgersen ML. 2010. Endocytosis and retrograde transport of Shiga toxin. Toxicon 56:1181–1185. [PubMed][CrossRef]
70. McCluskey AJ, Poon GM, Bolewska-Pedyczak E, Srikumar T, Jeram SM, Raught B, Gariepy J. 2008. The catalytic subunit of Shiga-like toxin 1 interacts with ribosomal stalk proteins and is inhibited by their conserved C-terminal domain. J Mol Biol 378:375–386. [PubMed][CrossRef]
71. Endo Y, Tsurugi K, Yutsudo T, Takeda Y, Ogasawara T, Igarashi K. 1988. Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and of Shiga toxin on eukaryotic ribosomes. RNA N-glycosidase activity of the toxins. Eur J Biochem 171:4–50. [PubMed][CrossRef]
72. Obrig TG, Moran TP, Brown JE. 1987. The mode of action of Shiga toxin on peptide elongation of eukaryotic protein synthesis. Biochem J 244:287–294. [PubMed]
73. Obrig TG, Del Vecchio PJ, Brown JE, Moran TP, Rowland BM, Judge TK, Rothman SW. 1988. Direct cytotoxic action of Shiga toxin on human vascular endothelial cells. Infect Immun 56:2373–2378. [PubMed]
74. Jandhyala DM, Ahluwalia A, Obrig T, Thorpe CM. 2008. ZAK: a MAP3Kinase that transduces Shiga toxin- and ricin-induced proinflammatory cytokine expression. Cell Microbiol 10:1468–1477. [PubMed][CrossRef]
75. Iordanov MS, Pribnow D, Magun JL, Dinh TH, Pearson JA, Chen SL, Magun BE. 1997. Ribotoxic stress response: activation of the stress-activated protein kinase JNK1 by inhibitors of the peptidyl transferase reaction and by sequence-specific RNA damage to the alpha-sarcin/ricin loop in the 28S rRNA. Mol Cell Biol 17:3373–3381. [PubMed]
76. Walchli S, Aasheim HC, Skanland SS, Spilsberg B, Torgersen ML, Rosendal KR, Sandvig K. 2009. Characterization of clathrin and Syk interaction upon Shiga toxin binding. Cell Signal 21:1161–1168. [PubMed][CrossRef]
77. Nakao H, Takeda T. 2000. Escherichia coli Shiga toxin. J Nat Toxins 9:299–313. [PubMed]
78. Orth D, Grif K, Khan AB, Naim A, Dierich MP, Wurzner R. 2007. The Shiga toxin genotype rather than the amount of Shiga toxin or the cytotoxicity of Shiga toxin in vitro correlates with the appearance of the hemolytic uremic syndrome. Diagn Microbiol Infect Dis 59:235–242. [PubMed][CrossRef]
79. Scheiring J, Andreoli SP Zimmerhackl LB. 2008. Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS). Pediatr Nephrol 23:1749–1760. [PubMed][CrossRef]
80. Allison HE. 2007. Stx-phages: drivers and mediators of the evolution of STEC and STEC-like pathogens. Future Microbiol 2:165–174. [PubMed][CrossRef]
81. Herold S, Karch H, Schmidt H. 2004. Shiga toxin-encoding bacteriophages—genomes in motion. Int J Med Microbiol 294:115–121. [PubMed][CrossRef]
82. Fuller CA, Pellino CA, Flagler MJ, Strasser JE, Weiss AA. Shiga toxin subtypes display dramatic differences in potency. Infect Immun 79:1329–1337. [PubMed][CrossRef]
83. de Sablet T, Bertin Y, Vareille M, Girardeau JP, Garrivier A, Gobert AP, Martin C. 2008. Differential expression of stx2 variants in Shiga toxin-producing Escherichia coli belonging to seropathotypes A and C. Microbiology 154:176–186. [PubMed][CrossRef]
84. 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 181:664–670. [PubMed][CrossRef]
85. Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI. 2000. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 342:1930–1936. [PubMed][CrossRef]
86. Johnson JR, Russo TA, Tarr PI, Carlino U, Bilge SS, Vary JC, Jr, Stell AL. 2000. Molecular epidemiological and phylogenetic associations of two novel putative virulence genes, iha and iroN( E. coli), among Escherichia coli isolates from patients with urosepsis. Infect Immun 68:3040–3047. [PubMed][CrossRef]
87. Toma C, Martinez Espinosa E, 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. [PubMed][CrossRef]
88. Johnson JR, Jelacic S, Schoening LM, Clabots C, Shaikh N, Mobley HL, Tarr PI. 2005. The IrgA homologue adhesin Iha is an Escherichia coli virulence factor in murine urinary tract infection. Infect Immun 73:965–971. [PubMed][CrossRef]
89. Postle K, Kadner RJ. 2003. Touch and go: tying TonB to transport. Mol Microbiol 49:869–882. [PubMed][CrossRef]
90. Rashid RA, Tarr PI, Moseley SL. 2006. Expression of the Escherichia coli IrgA homolog adhesin is regulated by the ferric uptake regulation protein. Microb Pathog 41:207–217. [PubMed][CrossRef]
91. Litwin CM, Calderwood SB. 1993. Role of iron in regulation of virulence genes. Clin Microbiol Rev 6:137–149. [PubMed]
92. Touati D. 2000. Iron and oxidative stress in bacteria. Arch Biochem Biophys 373:1–6. [PubMed][CrossRef]
93. Herold S, Paton JC, Srimanote P, Paton AW. 2009. Differential effects of short-chain fatty acids and iron on expression of iha in Shiga-toxigenic Escherichia coli. Microbiology 155:3554–3563. [PubMed][CrossRef]
94. Ewers C, Li G, Wilking H, Kiessling S, Alt K, Antao EM, Laturnus C, Diehl I, Glodde S, Homeier T, Bohnke U, Steinruck H, Philipp HC, aWieler LH. 2007. Avian pathogenic, uropathogenic, and newborn meningitis-causing Escherichia coli: how closely related are they? Int J Med Microbiol 297:163–176. [PubMed][CrossRef]
95. Ons E, Bleyen N, Tuntufye HN, Vandemaele F, Goddeeris BM. 2007. High prevalence iron receptor genes of avian pathogenic Escherichia coli. Avian Pathol 36:411–414. [PubMed][CrossRef]
96. Rodriguez-Siek KE, Giddings CW, Doetkott C, Johnson TJ, Fakhr MK, Nolan LK. 2005. Comparison of Escherichia coli isolates implicated in human urinary tract infection and avian colibacillosis. Microbiology 151:2097–2110. [PubMed][CrossRef]
97. Baumler AJ, Heffron F. 1995. Identification and sequence analysis of lpfABCDE, a putative fimbrial operon of Salmonella typhimurium. J Bacteriol 177:2087–2097. [PubMed]
98. Torres AG, Kanack KJ, Tutt CB, Popov V, Kaper JB. 2004. Characterization of the second long polar (LP) fimbriae of Escherichia coli O157:H7 and distribution of LP fimbriae in other pathogenic E. coli strains. FEMS Microbiol Lett 238:333–344. [PubMed]
99. Jordan DM, Cornick N, Torres AG, Dean-Nystrom EA, Kaper JB, Moon HW. 2004. Long polar fimbriae contribute to colonization by Escherichia coli O157:H7 in vivo. Infect Immun 72:6168–6171. [PubMed][CrossRef]
100. Torres AG, Milflores-Flores L, Garcia-Gallegos JG, Patel SD, Best A, La Ragione RM, Martinez-Laguna Y, Woodward MJ. 2007. Environmental regulation and colonization attributes of the long polar fimbriae (LPF) of Escherichia coli O157:H7. Int J Med Microbiol 297:177–185. [PubMed][CrossRef]
101. Torres AG, Giron JA, Perna NT, Burland V, Blattner FR, Avelino-Flores F, Kaper JB. 2002. Identification and characterization of lpfABCC'DE, a fimbrial operon of enterohemorrhagic Escherichia coli O157:H7. Infect Immun 70:5416–5427. [PubMed][CrossRef]
102. Farfan MJ, Cantero L, Vidal R, Botkin DJ, Torres AG. 2011. Long polar fimbriae of enterohemorrhagic Escherichia coli O157:H7 bind to extracellular matrix proteins. Infect Immun 79:3744–3750. [PubMed][CrossRef]
103. Torres AG, Kaper JB. 2003. Multiple elements controlling adherence of enterohemorrhagic Escherichia coli O157:H7 to HeLa cells. Infect Immun 71:4985–4995. [CrossRef]
104. Doughty S, Sloan J, Bennett-Wood V, Robertson M, Robins-Browne RM, Hartland EL. 2002. Identification of a novel fimbrial gene cluster related to long polar fimbriae in locus of enterocyte effacement-negative strains of enterohemorrhagic Escherichia coli. Infect Immun 70:6761–6769. [PubMed][CrossRef]
105. Lloyd SJ, Ritchie JM, Torres AG. 2012. Fimbriation and curliation in Escherichia coli O157:H7: a paradigm of intestinal and environmental colonization. Gut Microbes 3:272–276. [PubMed][CrossRef]
106. Bockemuhl J, Aleksic S, Karch H. 1992. Serological and biochemical properties of Shiga-like toxin (verocytotoxin)-producing strains of Escherichia coli, other than O-group 157, from patients in Germany. Zentralbl Bakteriol 276:189–195. [PubMed][CrossRef]
107. Mellmann A, Lu S, Karch H, Xu JG, Harmsen D, Schmidt MA, Bielaszewska M. 2008. Recycling of Shiga toxin 2 genes in sorbitol-fermenting enterohemorrhagic Escherichia coli O157:NM. Appl Environ Microbiol 74:67–72. [PubMed][CrossRef]
108. Boudailliez B, Berquin P, Mariani-Kurkdjian P, Ilef D, Cuvelier B, Capek I, Tribout B, Bingen E, Piussan C. 1997. Possible person-to-person transmission of Escherichia coli O111–associated hemolytic uremic syndrome. Pediatr Nephrol 11:36–39. [PubMed][CrossRef]
109. Morabito S, Karch H, Mariani-Kurkdjian P, Schmidt H, Minelli F, Bingen E, Caprioli A. 1998. Enteroaggregative, Shiga toxin-producing Escherichia coli O111:H2 associated with an outbreak of hemolytic-uremic syndrome. J Clin Microbiol 36:840–842. [PubMed]
110. Willshaw GA, Scotland SM, Smith HR, Rowe B. 1992. Properties of Vero cytotoxin-producing Escherichia coli of human origin of O serogroups other than O157. J Infect Dis 166:797–802. [PubMed][CrossRef]
111. Iyoda S, Terajima J, Wada A, Izumiya H, Tamura K, Watanabe H. 2000. Molecular epidemiology of enterohemorrhagic Escherichia coli. Nihon Saikingaku Zasshi 55:29–36. [PubMed][CrossRef]
112. Estrada-Garcia T, Navarro-Garcia F. 2012. Enteroaggregative Escherichia coli pathotype: a genetically heterogeneous emerging foodborne enteropathogen. FEMS Immunol Med Microbiol 66:281–298. [PubMed][CrossRef]
113. Smith HR, Cheasty T, Rowe B. 1997. Enteroaggregative Escherichia coli and outbreaks of gastroenteritis in UK. Lancet 350:814–815. [PubMed][CrossRef]
114. Tompkins DS, Hudson MJ, Smith HR, Eglin RP, Wheeler JG, Brett MM, Owen RJ, Brazier JS, Cumberland P, King V, Cook PE. 1999. A study of infectious intestinal disease in England: microbiological findings in cases and controls. Commun Dis Public Health 2:108–113. [PubMed]
115. Pabst WL, Altwegg M, Kind C, Mirjanic S, Hardegger D, Nadal D. 2003. Prevalence of enteroaggregative Escherichia coli among children with and without diarrhea in Switzerland. J Clin Microbiol 41:2289–2293. [PubMed][CrossRef]
116. Itoh Y, Nagano I, Kunishima M, Ezaki T. 1997. Laboratory investigation of enteroaggregative Escherichia coli O untypeable:H10 associated with a massive outbreak of gastrointestinal illness. J Clin Microbiol 35:2546–2550. [PubMed]
117. Harrington SM, Dudley EG, Nataro JP. 2006. Pathogenesis of enteroaggregative Escherichia coli infection. FEMS Microbiol Lett 254:12–18. [PubMed][CrossRef]
118. Czeczulin JR, Whittam TS, Henderson IR, Navarro-Garcia F, Nataro JP. 1999. Phylogenetic analysis of enteroaggregative and diffusely adherent Escherichia coli. Infect Immun 67:2692–2699. [PubMed]
119. Okeke IN, Wallace-Gadsden F, Simons HR, Matthews N, Labar AS, Hwang J, Wain J. 2010. Multi-locus sequence typing of enteroaggregative Escherichia coli isolates from Nigerian children uncovers multiple lineages. PLoS One 5:e14093. [PubMed][CrossRef]
120. Gallegos MT, Michan C, Ramos JL. 1993. The XylS/AraC family of regulators. Nucleic Acids Res 21:807–810. [PubMed][CrossRef]
121. Jiang ZD, Greenberg D, Nataro JP, Steffen R, DuPont HL. 2002. Rate of occurrence and pathogenic effect of enteroaggregative Escherichia coli virulence factors in international travelers. J Clin Microbiol 40:4185–4190. [PubMed][CrossRef]
122. Huang DB, Mohamed JA, Nataro JP, DuPont HL, Jiang ZD, Okhuysen PC. 2007. Virulence characteristics and the molecular epidemiology of enteroaggregative Escherichia coli isolates from travellers to developing countries. J Med Microbiol 56:1386–1392. [PubMed][CrossRef]
123. Sheikh J, Czeczulin JR, Harrington S, Hicks S, Henderson IR, Le Bouguenec C, Gounon P, Phillips A, Nataro JP. 2002. A novel dispersin protein in enteroaggregative Escherichia coli. J Clin Invest 110:1329–1337. [PubMed][CrossRef]
124. Nishi J, Sheikh J, Mizuguchi K, Luisi B, Burland V, Boutin A, Rose DJ, Blattner FR, Nataro JP. 2003. The export of coat protein from enteroaggregative Escherichia coli by a specific ATP-binding cassette transporter system. J Biol Chem 278:45680–45689. [PubMed][CrossRef]
125. Dudley EG, Thomson NR, Parkhill J, Morin NP, Nataro JP. 2006. Proteomic and microarray characterization of the AggR regulon identifies a pheU pathogenicity island in enteroaggregative Escherichia coli. Mol Microbiol 61:1267–1282. [PubMed][CrossRef]
126. Knutton S, Shaw RK, Bhan MK, Smith HR, McConnell MM, Cheasty T, Williams PH, Baldwin TJ. 1992. Ability of enteroaggregative Escherichia coli strains to adhere in vitro to human intestinal mucosa. Infect Immun 60:2083–2091. [PubMed]
127. Suzart S, Guth BE, Pedroso MZ, Okafor UM, Gomes TA. 2001. Diversity of surface structures and virulence genetic markers among enteroaggregative Escherichia coli (EAEC) strains with and without the EAEC DNA probe sequence. FEMS Microbiol Lett 201:163–168. [PubMed][CrossRef]
128. Vial PA, Robins-Browne R, Lior H, Prado V, Kaper JB, Nataro JP, Maneval D, Elsayed A, Levine MM. 1988. Characterization of enteroadherent-aggregative Escherichia coli, a putative agent of diarrheal disease. J Infect Dis 158:70–79. [PubMed][CrossRef]
129. Czeczulin JR, Balepur S, Hicks S, Phillips A, Hall R, Kothary MH, Navarro-Garcia F, Nataro JP. 1997. Aggregative adherence fimbria II, a second fimbrial antigen mediating aggregative adherence in enteroaggregative Escherichia coli. Infect Immun 65:4135–4145. [PubMed]
130. Velarde JJ, Varney KM, Inman KG, Farfan M, Dudley E, Fletcher J, Weber DJ, Nataro JP. 2007. Solution structure of the novel dispersin protein of enteroaggregative Escherichia coli. Mol Microbiol 66:1123–1135. [PubMed][CrossRef]
131. Rossiter AE, Browning DF, Leyton DL, Johnson MD, Godfrey RE, Wardius CA, Desvaux M, Cunningham AF, Ruiz-Perez F, Nataro JP, Busby SJ, and Henderson IR. 2011. Transcription of the plasmid-encoded toxin gene from enteroaggregative Escherichia coli is regulated by a novel co-activation mechanism involving CRP and Fis. Mol Microbiol 81:179–191. [PubMed][CrossRef]
132. Morin N, Santiago AE, Ernst RK, Guillot SJ, Nataro JP. 2013. Characterization of the AggR regulon in enteroaggregative Escherichia coli. Infect Immun 81:122–132. [PubMed][CrossRef]
133. Huang DB, DuPont HL, Jiang ZD, Carlin L, Okhuysen PC. 2004. Interleukin-8 response in an intestinal HCT-8 cell line infected with enteroaggregative and enterotoxigenic Escherichia coli. Clin Diagn Lab Immunol 11:548–551. [PubMed]
134. Harrington SM, Strauman MC, Abe CM, Nataro JP. 2005. Aggregative adherence fimbriae contribute to the inflammatory response of epithelial cells infected with enteroaggregative Escherichia coli. Cell Microbiol 7:1565–1578. [PubMed][CrossRef]
135. Henderson IR, Navarro-Garcia F, Desvaux M, Fernandez RC, Ala'Aldeen D. 2004. Type V protein secretion pathway: the autotransporter story. Microbiol Mol Biol Rev 68:692–744. [PubMed][CrossRef]
136. Navarro-Garcia F, Elias WP. 2011. Autotransporters and virulence of enteroaggregative E. coli. Gut Microbes 2:13–24. [PubMed][CrossRef]
137. Dautin N, Bernstein HD. 2007. Protein secretion in gram-negative bacteria via the autotransporter pathway. Annu Rev Microbiol 61:89–112. [PubMed][CrossRef]
138. Dutta S, Lalitha PV, Ware LA, Barbosa A, Moch JK, Vassell MA, Fileta BB, Kitov S, Kolodny N, Heppner DG, Haynes JD, Lanar DE. 2002. Purification, characterization, and immunogenicity of the refolded ectodomain of the Plasmodium falciparum apical membrane antigen 1 expressed in Escherichia coli. Infect Immun 70:3101–3110. [PubMed][CrossRef]
139. Canizalez-Roman A, Navarro-Garcia F. 2003. Fodrin CaM-binding domain cleavage by Pet from enteroaggregative Escherichia coli leads to actin cytoskeletal disruption. Mol Microbiol 48:947–958. [PubMed][CrossRef]
140. Navarro-Garcia F, Canizalez-Roman A, Luna J, Sears C, Nataro JP. 2001. Plasmid-encoded toxin of enteroaggregative Escherichia coli is internalized by epithelial cells. Infect Immun 69:1053–1060. [PubMed][CrossRef]
141. Henderson IR, Czeczulin J, Eslava C, Noriega F, Nataro JP. 1999. Characterization of pic, a secreted protease of Shigella flexneri and enteroaggregative Escherichia coli. Infect Immun 67:5587–5596. [PubMed]
142. Harrington SM, Sheikh J, Henderson IR, Ruiz-Perez F, Cohen PS, Nataro JP. 2009. The Pic protease of enteroaggregative Escherichia coli promotes intestinal colonization and growth in the presence of mucin. Infect Immun 77:2465–2473. [PubMed][CrossRef]
143. Boisen N, Ruiz-Perez F, Scheutz F, Krogfelt KA, Nataro JP. 2009. Short report: high prevalence of serine protease autotransporter cytotoxins among strains of enteroaggregative Escherichia coli. Am J Trop Med Hyg 80:294–301. [PubMed]
144. Rajakumar K, Sasakawa C, Adler B. 1997. Use of a novel approach, termed island probing, identifies the Shigella flexneri she pathogenicity island which encodes a homolog of the immunoglobulin A protease-like family of proteins. Infect Immun 65:4606–4614. [PubMed]
145. Ruiz-Perez F, Wahid R, Faherty CS, Kolappaswamy K, Rodriguez L, Santiago A, Murphy E, Cross A, Sztein MB, Nataro JP. 2011. Serine protease autotransporters from Shigellaflexneri and pathogenic Escherichia coli target a broad range of leukocyte glycoproteins. Proc Natl Acad Sci USA 108:12881–12886. [PubMed][CrossRef]
146. Provence DL, Curtiss R, 3rd. 1994. Isolation and characterization of a gene involved in hemagglutination by an avian pathogenic Escherichia coli strain. Infect Immun 62:1369–1380. [PubMed]
147. Benjelloun-Touimi Z, Si Tahar M, Montecucco C, Sansonetti PJ, Parsot C. 1998. SepA, the 110 kDa protein secreted by Shigella flexneri: two-domain structure and proteolytic activity. Microbiology 144(Pt 7):1815–1822. [PubMed][CrossRef]
148. Al-Hasani K, Henderson IR, Sakellaris H, Rajakumar K, Grant T, Nataro JP, Robins-Browne R, Adler B. 2000. The sigA gene which is borne on the she pathogenicity island of Shigella flexneri 2a encodes an exported cytopathic protease involved in intestinal fluid accumulation. Infect Immun 68:2457–2463. [PubMed][CrossRef]
149. Navarro-Garcia F, Sears C, Eslava C, Cravioto A, Nataro JP. 1999. Cytoskeletal effects induced by pet, the serine protease enterotoxin of enteroaggregative Escherichia coli. Infect Immun 67:2184–2192. [PubMed]
150. Navarro-Garcia F, Canizalez-Roman A, Burlingame KE, Teter K, Vidal JE. 2007. Pet, a non-AB toxin, is transported and translocated into epithelial cells by a retrograde trafficking pathway. Infect Immun 75:2101–2109. [PubMed][CrossRef]
151. Navarro-Garcia F, Canizalez-Roman A, Vidal JE, Salazar MI. 2007. Intoxication of epithelial cells by plasmid-encoded toxin requires clathrin-mediated endocytosis. Microbiology 153:2828–2838. [PubMed][CrossRef]
152. Fasano A, Noriega FR, Maneval DR, Jr, Chanasongcram S, Russell R, Guandalini S, Levine MM. 1995. Shigella enterotoxin 1: an enterotoxin of Shigella flexneri 2a active in rabbit small intestine in vivo and in vitro. J Clin Invest 95:2853–2861. [PubMed][CrossRef]

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A major outbreak caused by of serotype O104:H4 spread throughout Europe in 2011. This large outbreak was caused by an unusual strain that is most similar to enteroaggregative (EAEC) of serotype O104:H4. A significant difference, however, is the presence of a prophage encoding the Shiga toxin, which is characteristic of enterohemorrhagic (EHEC) strains. This combination of genomic features, associating characteristics from both EAEC and EHEC, represents a new pathotype. The 2011 O104:H4 outbreak of hemorrhagic diarrhea in Germany is an example of the explosive cocktail of high virulence and resistance that can emerge in this species. A total of 46 deaths, 782 cases of hemolytic-uremic syndrome, and 3,128 cases of acute gastroenteritis were attributed to this new clone of EAEC/EHEC. In addition, recent identification in France of similar O104:H4 clones exhibiting the same virulence factors suggests that the EHEC O104:H4 pathogen has become endemically established in Europe after the end of the outbreak. EAEC strains of serotype O104:H4 contain a large set of virulence-associated genes regulated by the AggR transcription factor. They include, among other factors, the pAA plasmid genes encoding the aggregative adherence fimbriae, which anchor the bacterium to the intestinal mucosa (stacked-brick adherence pattern on epithelial cells). Furthermore, sequencing studies showed that horizontal genetic exchange allowed for the emergence of the highly virulent Shiga toxin-producing EAEC O104:H4 strain that caused the German outbreak. This article discusses the role these virulence factors could have in EAEC/EHEC O104:H4 pathogenesis.

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Hybrid characteristics of O104:H4 outbreak strain (EAEC/STEC). Schematic representation of the genes harbored by O104:H4; the main genes from EAEC or STEC are highlighted: (coding for Stx 2), , , and (coding for the SPATE proteins); Pic, protein involved in intestinal colonization; SigA, a homolog of Pet, with cytotoxic activity; SepA, a colonization factor of ), (coding for ShET1, a holotoxin AB5), (coding for Iha, a STEC adhesin that is an IrgA homolog), , , , (genes from EAEC plasmids coding for transcription regulator, AAF/I, dispersin, and dispersin transporter, respectively), (coding for Lpf of STEC), (coding for a cluster for Tellurite resistance), CTX-M15 and TEM-1 (antibiotic resistance genes). SigA and SepA are SPATEs detected mainly in sp.

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.EHEC-0008-2013
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Adherence patterns of EAEC, STEC, and O104:H4 outbreak strain to epithelial cells. Subconfluent epithelial cell cultures are infected with the different bacterial strains. Cells are fixed and stained with Giemsa stain. From Scalesky et al. 1999. 3410; Paton et al. 2001. 6999; and Martina Bielaszewska. http://ecdc.europa.eu/en/press/events/Documents/22-231111-Breakthroughs-in-molecular-epidemiology-Bielaszewska.pdf.

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.EHEC-0008-2013
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Transmission electron microscopy (TEM) of Stx2 phage (P13374) induction from lysogenic strain K-12 strain TPE2364 (C600) infected with phage lysates of O104:H4 strain CB13374. (A, B) Ultrathin sections of two bacterial cells (TPE2364) with maturating virion particles within the cytoplasm indicated by arrows (bars, 500 nm). (C) TEM of CsCl-purified, negatively stained phage (P13374) particles released by strain TPE2364 (bar, 100 nm). Short tails (arrows) and a hexagonal head are shown. From Beutin et al. 2012. 10444.

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.EHEC-0008-2013
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Schematic representation of O104:H4 virulence factors and their targets on the mucosal epithelium. The targets and virulence factors are extrapolated from their known function in other pathogens, and the action mechanism for ShET1 is hypothetical.

Source: microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.EHEC-0008-2013
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