Microbiology, pathogenesis, epidemiology, and prevention of enterohemorrhagic Escherichia coli (EHEC)
- Stephen B Calderwood, MD
Stephen B Calderwood, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine (Microbiology and Immunobiology)
- Harvard Medical School
- Section Editors
- Daniel J Sexton, MD
Daniel J Sexton, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine
- Duke University Medical Center
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
Enterohemorrhagic E. coli (EHEC) are strains capable of producing Shiga toxin and typically cause bloody diarrhea [1-3]. Hemolytic-uremic syndrome complicates 6 to 9 percent of EHEC infections overall and about 15 percent of EHEC infections in children under age 10 [3-6]. Since the initial recognition of severe bloody diarrhea due to a new serotype of E. coli, O157:H7, in the United States in 1982, outbreaks and sporadic infections have been attributed to EHEC worldwide [4,5,7-22].
The microbiology, pathogenesis, epidemiology, and prevention of EHEC will be reviewed here. The clinical manifestations, diagnosis, and treatment of EHEC infections are discussed separately. (See "Clinical manifestations, diagnosis and treatment of enterohemorrhagic Escherichia coli (EHEC) infection".)
E. coli strains can be classified by their O and H antigens [23-25]. The O antigen is defined serologically and determined by the repeating polysaccharide chains that are part of the lipopolysaccharide (LPS) embedded in the outer leaflet of the outer membrane. The H antigen is defined serologically by the antigenic specificity of the bacterial flagellum.
EHEC strains of E. coli contain specific virulence properties: lysogenic phage encoding one or more Shiga toxins (with or without a chromosomal pathogenicity island), and often an additional virulence plasmid. These strains are also referred to as Shiga-toxin producing E. coli, or STEC.
In the United States, many EHEC strains are serotype O157:H7 . Non-O157 serotypes have also been described in the United States and in other countries; infections due to non-O157 serotypes are estimated to account for 60 percent of EHEC infections in the United States [21,26-28]. Among 940 human non-O157 STEC isolates submitted to the Centers for Disease Control (CDC) between 1983 and 2002, the most common serogroups were O26, O111, O103, O121, O45, and O145 (22, 16, 12, 8, 7, and 5 percent, respectively) .
- Levine MM. Escherichia coli that cause diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherent. J Infect Dis 1987; 155:377.
- O'Brien AO, Lively TA, Chen ME, et al. Escherichia coli O157:H7 strains associated with haemorrhagic colitis in the United States produce a Shigella dysenteriae 1 (SHIGA) like cytotoxin. Lancet 1983; 1:702.
- Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005; 365:1073.
- Boyce TG, Swerdlow DL, Griffin PM. Escherichia coli O157:H7 and the hemolytic-uremic syndrome. N Engl J Med 1995; 333:364.
- Bell BP, Goldoft M, Griffin PM, et al. A multistate outbreak of Escherichia coli O157:H7-associated bloody diarrhea and hemolytic uremic syndrome from hamburgers. The Washington experience. JAMA 1994; 272:1349.
- Page AV, Liles WC. Enterohemorrhagic Escherichia coli Infections and the Hemolytic-Uremic Syndrome. Med Clin North Am 2013; 97:681.
- Su C, Brandt LJ. Escherichia coli O157:H7 infection in humans. Ann Intern Med 1995; 123:698.
- Waters JR, Sharp JC, Dev VJ. Infection caused by Escherichia coli O157:H7 in Alberta, Canada, and in Scotland: a five-year review, 1987-1991. Clin Infect Dis 1994; 19:834.
- Tarr PI. Escherichia coli O157:H7: clinical, diagnostic, and epidemiological aspects of human infection. Clin Infect Dis 1995; 20:1.
- Noël JM, Boedeker EC. Enterohemorrhagic Escherichia coli: a family of emerging pathogens. Dig Dis 1997; 15:67.
- Slutsker L, Ries AA, Greene KD, et al. Escherichia coli O157:H7 diarrhea in the United States: clinical and epidemiologic features. Ann Intern Med 1997; 126:505.
- Dundas S, Todd WT, Stewart AI, et al. The central Scotland Escherichia coli O157:H7 outbreak: risk factors for the hemolytic uremic syndrome and death among hospitalized patients. Clin Infect Dis 2001; 33:923.
- Slutsker L, Ries AA, Maloney K, et al. A nationwide case-control study of Escherichia coli O157:H7 infection in the United States. J Infect Dis 1998; 177:962.
- Jay MT, Garrett V, Mohle-Boetani JC, et al. A multistate outbreak of Escherichia coli O157:H7 infection linked to consumption of beef tacos at a fast-food restaurant chain. Clin Infect Dis 2004; 39:1.
- Cody SH, Glynn MK, Farrar JA, et al. An outbreak of Escherichia coli O157:H7 infection from unpasteurized commercial apple juice. Ann Intern Med 1999; 130:202.
- Fukushima H, Hashizume T, Morita Y, et al. Clinical experiences in Sakai City Hospital during the massive outbreak of enterohemorrhagic Escherichia coli O157 infections in Sakai City, 1996. Pediatr Int 1999; 41:213.
- Centers for Disease Control and Prevention (CDC). Escherichia coli O157:H7 infection associated with drinking raw milk--Washington and Oregon, November-December 2005. MMWR Morb Mortal Wkly Rep 2007; 56:165.
- Crump JA, Sulka AC, Langer AJ, et al. An outbreak of Escherichia coli O157:H7 infections among visitors to a dairy farm. N Engl J Med 2002; 347:555.
- Varma JK, Greene KD, Reller ME, et al. An outbreak of Escherichia coli O157 infection following exposure to a contaminated building. JAMA 2003; 290:2709.
- Bender JB, Hedberg CW, Besser JM, et al. Surveillance by molecular subtype for Escherichia coli O157:H7 infections in Minnesota by molecular subtyping. N Engl J Med 1997; 337:388.
- Elliott EJ, Robins-Browne RM, O'Loughlin EV, et al. Nationwide study of haemolytic uraemic syndrome: clinical, microbiological, and epidemiological features. Arch Dis Child 2001; 85:125.
- Centers for Disease Control and Prevention (CDC). Multistate outbreak of Escherichia coli O157:H7 infections associated with eating ground beef--United States, June-July 2002. MMWR Morb Mortal Wkly Rep 2002; 51:637.
- Blattner FR, Plunkett G 3rd, Bloch CA, et al. The complete genome sequence of Escherichia coli K-12. Science 1997; 277:1453.
- Perna NT, Plunkett G 3rd, Burland V, et al. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 2001; 409:529.
- Hayashi T, Makino K, Ohnishi M, et al. Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res 2001; 8:11.
- Mead PS, Slutsker L, Dietz V, et al. Food-related illness and death in the United States. Emerg Infect Dis 1999; 5:607.
- Johnson KE, Thorpe CM, Sears CL. The emerging clinical importance of non-O157 Shiga toxin-producing Escherichia coli. Clin Infect Dis 2006; 43:1587.
- Pai CH, Ahmed N, Lior H, et al. Epidemiology of sporadic diarrhea due to verocytotoxin-producing Escherichia coli: a two-year prospective study. J Infect Dis 1988; 157:1054.
- Brooks JT, Sowers EG, Wells JG, et al. Non-O157 Shiga toxin-producing Escherichia coli infections in the United States, 1983-2002. J Infect Dis 2005; 192:1422.
- Werber D, Fruth A, Heissenhuber A, et al. Shiga toxin-producing Escherichia coli O157 more frequently cause bloody diarrhea than do non-O157 strains. J Infect Dis 2004; 189:1335.
- Piercefield EW, Bradley KK, Coffman RL, Mallonee SM. Hemolytic Uremic Syndrome After an Escherichia coli O111 Outbreak. Arch Intern Med 2010; 170:1656.
- Frank C, Werber D, Cramer JP, et al. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med 2011; 365:1771.
- Bielaszewska M, Mellmann A, Zhang W, et al. Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. Lancet Infect Dis 2011; 11:671.
- Rasko DA, Webster DR, Sahl JW, et al. Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany. N Engl J Med 2011; 365:709.
- Rohde H, Qin J, Cui Y, et al. Open-source genomic analysis of Shiga-toxin-producing E. coli O104:H4. N Engl J Med 2011; 365:718.
- Schroeder CM, Zhao C, DebRoy C, et al. Antimicrobial resistance of Escherichia coli O157 isolated from humans, cattle, swine, and food. Appl Environ Microbiol 2002; 68:576.
- Jarvis KG, Kaper JB. Secretion of extracellular proteins by enterohemorrhagic Escherichia coli via a putative type III secretion system. Infect Immun 1996; 64:4826.
- Mecsas JJ, Strauss EJ. Molecular mechanisms of bacterial virulence: type III secretion and pathogenicity islands. Emerg Infect Dis 1996; 2:270.
- Abe A, Heczko U, Hegele RG, Brett Finlay B. Two enteropathogenic Escherichia coli type III secreted proteins, EspA and EspB, are virulence factors. J Exp Med 1998; 188:1907.
- Galán JE, Collmer A. Type III secretion machines: bacterial devices for protein delivery into host cells. Science 1999; 284:1322.
- Santos AS, Finlay BB. Bringing down the host: enteropathogenic and enterohaemorrhagic Escherichia coli effector-mediated subversion of host innate immune pathways. Cell Microbiol 2015; 17:318.
- Finlay BB, Cossart P. Exploitation of mammalian host cell functions by bacterial pathogens. Science 1997; 276:718.
- Delahay RM, Knutton S, Shaw RK, et al. The coiled-coil domain of EspA is essential for the assembly of the type III secretion translocon on the surface of enteropathogenic Escherichia coli. J Biol Chem 1999; 274:35969.
- Knutton S, Rosenshine I, Pallen MJ, et al. A novel EspA-associated surface organelle of enteropathogenic Escherichia coli involved in protein translocation into epithelial cells. EMBO J 1998; 17:2166.
- Kenny B, DeVinney R, Stein M, et al. Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell 1997; 91:511.
- Robinson CM, Sinclair JF, Smith MJ, O'Brien AD. Shiga toxin of enterohemorrhagic Escherichia coli type O157:H7 promotes intestinal colonization. Proc Natl Acad Sci U S A 2006; 103:9667.
- McDaniel TK, Jarvis KG, Donnenberg MS, Kaper JB. A genetic locus of enterocyte effacement conserved among diverse enterobacterial pathogens. Proc Natl Acad Sci U S A 1995; 92:1664.
- Nataro JP, Kaper JB. Diarrheagenic Escherichia coli. Clin Microbiol Rev 1998; 11:142.
- Mellies JL, Elliott SJ, Sperandio V, et al. The Per regulon of enteropathogenic Escherichia coli : identification of a regulatory cascade and a novel transcriptional activator, the locus of enterocyte effacement (LEE)-encoded regulator (Ler). Mol Microbiol 1999; 33:296.
- Sperandio V, Mellies JL, Nguyen W, et al. Quorum sensing controls expression of the type III secretion gene transcription and protein secretion in enterohemorrhagic and enteropathogenic Escherichia coli. Proc Natl Acad Sci U S A 1999; 96:15196.
- Yang L, Li B, Zheng XY, et al. Salicylic acid biosynthesis is enhanced and contributes to increased biotrophic pathogen resistance in Arabidopsis hybrids. Nat Commun 2015; 6:7309.
- Calderwood SB, Acheson DWK, Keusch GT, et al. Proposed new nomenclature for SLT (VT) family. ASM News 1996; 62:118.
- Te Loo DM, van Hinsbergh VW, van den Heuvel LP, Monnens LA. Detection of verocytotoxin bound to circulating polymorphonuclear leukocytes of patients with hemolytic uremic syndrome. J Am Soc Nephrol 2001; 12:800.
- Ståhl AL, Arvidsson I, Johansson KE, et al. A novel mechanism of bacterial toxin transfer within host blood cell-derived microvesicles. PLoS Pathog 2015; 11:e1004619.
- Chandler WL, Jelacic S, Boster DR, et al. Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome. N Engl J Med 2002; 346:23.
- Sakiri R, Ramegowda B, Tesh VL. Shiga toxin type 1 activates tumor necrosis factor-alpha gene transcription and nuclear translocation of the transcriptional activators nuclear factor-kappaB and activator protein-1. Blood 1998; 92:558.
- Meuth SG, Göbel K, Kanyshkova T, et al. Thalamic involvement in patients with neurologic impairment due to Shiga toxin 2. Ann Neurol 2013; 73:419.
- Paton AW, Morona R, Paton JC. A new biological agent for treatment of Shiga toxigenic Escherichia coli infections and dysentery in humans. Nat Med 2000; 6:265.
- 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.
- Riley LW, Remis RS, Helgerson SD, et al. Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med 1983; 308:681.
- Crim SM, Iwamoto M, Huang JY, et al. Incidence and trends of infection with pathogens transmitted commonly through food--Foodborne Diseases Active Surveillance Network, 10 U.S. sites, 2006-2013. MMWR Morb Mortal Wkly Rep 2014; 63:328.
- Huang JY, Henao OL, Griffin PM, et al. Infection with Pathogens Transmitted Commonly Through Food and the Effect of Increasing Use of Culture-Independent Diagnostic Tests on Surveillance--Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2012-2015. MMWR Morb Mortal Wkly Rep 2016; 65:368.
- Rangel JM, Sparling PH, Crowe C, et al. Epidemiology of Escherichia coli O157:H7 outbreaks, United States, 1982-2002. Emerg Infect Dis 2005; 11:603.
- Ahn CK, Russo AJ, Howell KR, et al. Deer sausage: a newly identified vehicle of transmission of Escherichia coli O157:H7. J Pediatr 2009; 155:587.
- Guh A, Phan Q, Nelson R, et al. Outbreak of Escherichia coli O157 associated with raw milk, Connecticut, 2008. Clin Infect Dis 2010; 51:1411.
- Laidler MR, Tourdjman M, Buser GL, et al. Escherichia coli O157:H7 infections associated with consumption of locally grown strawberries contaminated by deer. Clin Infect Dis 2013; 57:1129.
- Centers for Disease Control and Prevention (CDC). Ongoing multistate outbreak of Escherichia coli serotype O157:H7 infections associated with consumption of fresh spinach--United States, September 2006. MMWR Morb Mortal Wkly Rep 2006; 55:1045.
- www.cdc.gov/foodborne/ecolispinach/100606.htm (Accessed on October 22, 2006).
- Wendel AM, Johnson DH, Sharapov U, et al. Multistate outbreak of Escherichia coli O157:H7 infection associated with consumption of packaged spinach, August-September 2006: the Wisconsin investigation. Clin Infect Dis 2009; 48:1079.
- Neil KP, Biggerstaff G, MacDonald JK, et al. A novel vehicle for transmission of Escherichia coli O157:H7 to humans: multistate outbreak of E. coli O157:H7 infections associated with consumption of ready-to-bake commercial prepackaged cookie dough--United States, 2009. Clin Infect Dis 2012; 54:511.
- Buchholz U, Bernard H, Werber D, et al. German outbreak of Escherichia coli O104:H4 associated with sprouts. N Engl J Med 2011; 365:1763.
- King LA, Nogareda F, Weill FX, et al. Outbreak of Shiga toxin-producing Escherichia coli O104:H4 associated with organic fenugreek sprouts, France, June 2011. Clin Infect Dis 2012; 54:1588.
- www.cdc.gov/ecoli/current.htm (Accessed on December 14, 2006).
- Raffaelli RM, Paladini M, Hanson H, et al. Child care-associated outbreak of Escherichia coli O157:H7 and hemolytic uremic syndrome. Pediatr Infect Dis J 2007; 26:951.
- Sin MA, Takla A, Flieger A, et al. Carrier prevalence, secondary household transmission, and long-term shedding in 2 districts during the Escherichia coli O104:H4 outbreak in Germany, 2011. J Infect Dis 2013; 207:432.
- Vonberg RP, Höhle M, Aepfelbacher M, et al. Duration of fecal shedding of Shiga toxin-producing Escherichia coli O104:H4 in patients infected during the 2011 outbreak in Germany: a multicenter study. Clin Infect Dis 2013; 56:1132.
- Steinmuller N, Demma L, Bender JB, et al. Outbreaks of enteric disease associated with animal contact: not just a foodborne problem anymore. Clin Infect Dis 2006; 43:1596.
- Keen JE, Wittum TE, Dunn JR, et al. Shiga-toxigenic Escherichia coli O157 in agricultural fair livestock, United States. Emerg Infect Dis 2006; 12:780.
- Centers for Disease Control and Prevention (CDC). Outbreaks of Escherichia coli O157:H7 associated with petting zoos--North Carolina, Florida, and Arizona, 2004 and 2005. MMWR Morb Mortal Wkly Rep 2005; 54:1277.
- Weese JS, McCarthy L, Mossop M, et al. Observation of practices at petting zoos and the potential impact on zoonotic disease transmission. Clin Infect Dis 2007; 45:10.
- Centers for Disease Control and Prevention (CDC). Notes from the field: Escherichia coli O157:H7 gastroenteritis associated with a State Fair - North Carolina, 2011. MMWR Morb Mortal Wkly Rep 2012; 60:1745.
- Centers for Disease Control and Prevention (CDC). Outbreak of Shiga toxin-producing Escherichia coli O111 infections associated with a correctional facility dairy - Colorado, 2010. MMWR Morb Mortal Wkly Rep 2012; 61:149.
- Banatvala N, Magnano AR, Cartter ML, et al. Meat grinders and molecular epidemiology: two supermarket outbreaks of Escherichia coli O157:H7 infection. J Infect Dis 1996; 173:480.
- Werber D, Mason BW, Evans MR, Salmon RL. Preventing household transmission of Shiga toxin-producing Escherichia coli O157 infection: promptly separating siblings might be the key. Clin Infect Dis 2008; 46:1189.
- Wells JG, Davis BR, Wachsmuth IK, et al. Laboratory investigation of hemorrhagic colitis outbreaks associated with a rare Escherichia coli serotype. J Clin Microbiol 1983; 18:512.
- Karch H, Rüssmann H, Schmidt H, et al. Long-term shedding and clonal turnover of enterohemorrhagic Escherichia coli O157 in diarrheal diseases. J Clin Microbiol 1995; 33:1602.
- Welinder-Olsson C, Kjellin E, Badenfors M, Kaijser B. Improved microbiological techniques using the polymerase chain reaction and pulsed-field gel electrophoresis for diagnosis and follow-up of enterohaemorrhagic Escherichia coli infection. Eur J Clin Microbiol Infect Dis 2000; 19:843.
- Seto EY, Soller JA, Colford JM Jr. Strategies to reduce person-to-person transmission during widespread Escherichia coli O157:H7 outbreak. Emerg Infect Dis 2007; 13:860.
- Belongia EA, Osterholm MT, Soler JT, et al. Transmission of Escherichia coli O157:H7 infection in Minnesota child day-care facilities. JAMA 1993; 269:883.