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. 1998 Apr-Jun;4(2):251–261. doi: 10.3201/eid0402.980212

Enteroaggregative Escherichia coli.

J P Nataro 1, T Steiner 1, R L Guerrant 1
PMCID: PMC2640136  PMID: 9621195

Abstract

Enteroaggregative Escherichia coli (EAEC), an increasingly recognized cause of diarrhea in children in developing countries, has been particularly associated with persistent diarrhea (more than 14 days), a major cause of illness and death. Recent outbreaks implicate EAEC as a cause of foodborne illness in industrialized countries. The pathogenesis of EAEC infection is not well understood, but a model can be proposed in which EAEC adhere to the intestinal mucosa and elaborate enterotoxins and cytotoxins, which result in secretory diarrhea and mucosal damage. EAEC's ability to stimulate the release of inflammatory mediators may also play a role in intestinal illness.

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Selected References

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  1. Baldwin T. J., Knutton S., Sellers L., Hernandez H. A., Aitken A., Williams P. H. Enteroaggregative Escherichia coli strains secrete a heat-labile toxin antigenically related to E. coli hemolysin. Infect Immun. 1992 May;60(5):2092–2095. doi: 10.1128/iai.60.5.2092-2095.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baudry B., Savarino S. J., Vial P., Kaper J. B., Levine M. M. A sensitive and specific DNA probe to identify enteroaggregative Escherichia coli, a recently discovered diarrheal pathogen. J Infect Dis. 1990 Jun;161(6):1249–1251. doi: 10.1093/infdis/161.6.1249. [DOI] [PubMed] [Google Scholar]
  3. Benjamin P., Federman M., Wanke C. A. Characterization of an invasive phenotype associated with enteroaggregative Escherichia coli. Infect Immun. 1995 Sep;63(9):3417–3421. doi: 10.1128/iai.63.9.3417-3421.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bhan M. K., Bhandari N., Sazawal S., Clemens J., Raj P., Levine M. M., Kaper J. B. Descriptive epidemiology of persistent diarrhoea among young children in rural northern India. Bull World Health Organ. 1989;67(3):281–288. [PMC free article] [PubMed] [Google Scholar]
  5. Bhan M. K., Khoshoo V., Sommerfelt H., Raj P., Sazawal S., Srivastava R. Enteroaggregative Escherichia coli and Salmonella associated with nondysenteric persistent diarrhea. Pediatr Infect Dis J. 1989 Aug;8(8):499–502. doi: 10.1097/00006454-198908000-00005. [DOI] [PubMed] [Google Scholar]
  6. Bhan M. K., Raj P., Levine M. M., Kaper J. B., Bhandari N., Srivastava R., Kumar R., Sazawal S. Enteroaggregative Escherichia coli associated with persistent diarrhea in a cohort of rural children in India. J Infect Dis. 1989 Jun;159(6):1061–1064. doi: 10.1093/infdis/159.6.1061. [DOI] [PubMed] [Google Scholar]
  7. Bhatnagar S., Bhan M. K., Sommerfelt H., Sazawal S., Kumar R., Saini S. Enteroaggregative Escherichia coli may be a new pathogen causing acute and persistent diarrhea. Scand J Infect Dis. 1993;25(5):579–583. doi: 10.3109/00365549309008546. [DOI] [PubMed] [Google Scholar]
  8. Bouzari S., Jafari A., Farhoudi-Moghaddam A. A., Shokouhi F., Parsi M. Adherence of non-enteropathogenic Escherichia coli to HeLa cells. J Med Microbiol. 1994 Feb;40(2):95–97. doi: 10.1099/00222615-40-2-95. [DOI] [PubMed] [Google Scholar]
  9. Checkley W., Gilman R. H., Epstein L. D., Suarez M., Diaz J. F., Cabrera L., Black R. E., Sterling C. R. Asymptomatic and symptomatic cryptosporidiosis: their acute effect on weight gain in Peruvian children. Am J Epidemiol. 1997 Jan 15;145(2):156–163. doi: 10.1093/oxfordjournals.aje.a009086. [DOI] [PubMed] [Google Scholar]
  10. Cobeljić M., Miljković-Selimović B., Paunović-Todosijević D., Velicković Z., Lepsanović Z., Zec N., Savić D., Ilić R., Konstantinović S., Jovanović B. Enteroaggregative Escherichia coli associated with an outbreak of diarrhoea in a neonatal nursery ward. Epidemiol Infect. 1996 Aug;117(1):11–16. doi: 10.1017/s0950268800001072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cravioto A., Tello A., Navarro A., Ruiz J., Villafán H., Uribe F., Eslava C. Association of Escherichia coli HEp-2 adherence patterns with type and duration of diarrhoea. Lancet. 1991 Feb 2;337(8736):262–264. doi: 10.1016/0140-6736(91)90868-p. [DOI] [PubMed] [Google Scholar]
  12. Czeczulin J. R., Balepur S., Hicks S., Phillips A., Hall R., Kothary M. H., Navarro-Garcia F., Nataro J. P. Aggregative adherence fimbria II, a second fimbrial antigen mediating aggregative adherence in enteroaggregative Escherichia coli. Infect Immun. 1997 Oct;65(10):4135–4145. doi: 10.1128/iai.65.10.4135-4145.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Debroy C., Yealy J., Wilson R. A., Bhan M. K., Kumar R. Antibodies raised against the outer membrane protein interrupt adherence of enteroaggregative Escherichia coli. Infect Immun. 1995 Aug;63(8):2873–2879. doi: 10.1128/iai.63.8.2873-2879.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fang G. D., Lima A. A., Martins C. V., Nataro J. P., Guerrant R. L. Etiology and epidemiology of persistent diarrhea in northeastern Brazil: a hospital-based, prospective, case-control study. J Pediatr Gastroenterol Nutr. 1995 Aug;21(2):137–144. doi: 10.1097/00005176-199508000-00003. [DOI] [PubMed] [Google Scholar]
  15. González R., Díaz C., Mariño M., Cloralt R., Pequeneze M., Pérez-Schael I. Age-specific prevalence of Escherichia coli with localized and aggregative adherence in Venezuelan infants with acute diarrhea. J Clin Microbiol. 1997 May;35(5):1103–1107. doi: 10.1128/jcm.35.5.1103-1107.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Guerrant R. L., Schorling J. B., McAuliffe J. F., de Souza M. A. Diarrhea as a cause and an effect of malnutrition: diarrhea prevents catch-up growth and malnutrition increases diarrhea frequency and duration. Am J Trop Med Hyg. 1992 Jul;47(1 Pt 2):28–35. doi: 10.4269/ajtmh.1992.47.28. [DOI] [PubMed] [Google Scholar]
  17. Henry F. J., Udoy A. S., Wanke C. A., Aziz K. M. Epidemiology of persistent diarrhea and etiologic agents in Mirzapur, Bangladesh. Acta Paediatr Suppl. 1992 Sep;381:27–31. doi: 10.1111/j.1651-2227.1992.tb12368.x. [DOI] [PubMed] [Google Scholar]
  18. Hicks S., Candy D. C., Phillips A. D. Adhesion of enteroaggregative Escherichia coli to pediatric intestinal mucosa in vitro. Infect Immun. 1996 Nov;64(11):4751–4760. doi: 10.1128/iai.64.11.4751-4760.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Huppertz H. I., Rutkowski S., Aleksic S., Karch H. Acute and chronic diarrhoea and abdominal colic associated with enteroaggregative Escherichia coli in young children living in western Europe. Lancet. 1997 Jun 7;349(9066):1660–1662. doi: 10.1016/S0140-6736(96)12485-5. [DOI] [PubMed] [Google Scholar]
  20. Kang G., Mathan M. M., Mathan V. I. Evaluation of a simplified HEp-2 cell adherence assay for Escherichia coli isolated from south Indian children with acute diarrhea and controls. J Clin Microbiol. 1995 Aug;33(8):2204–2205. doi: 10.1128/jcm.33.8.2204-2205.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Knutton S., Shaw R. K., Bhan M. K., Smith H. R., McConnell M. M., Cheasty T., Williams P. H., Baldwin T. J. Ability of enteroaggregative Escherichia coli strains to adhere in vitro to human intestinal mucosa. Infect Immun. 1992 May;60(5):2083–2091. doi: 10.1128/iai.60.5.2083-2091.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lima A. A., Fang G., Schorling J. B., de Albuquerque L., McAuliffe J. F., Mota S., Leite R., Guerrant R. L. Persistent diarrhea in northeast Brazil: etiologies and interactions with malnutrition. Acta Paediatr Suppl. 1992 Sep;381:39–44. doi: 10.1111/j.1651-2227.1992.tb12370.x. [DOI] [PubMed] [Google Scholar]
  23. Madara J. L., Patapoff T. W., Gillece-Castro B., Colgan S. P., Parkos C. A., Delp C., Mrsny R. J. 5'-adenosine monophosphate is the neutrophil-derived paracrine factor that elicits chloride secretion from T84 intestinal epithelial cell monolayers. J Clin Invest. 1993 May;91(5):2320–2325. doi: 10.1172/JCI116462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mahida Y. R., Makh S., Hyde S., Gray T., Borriello S. P. Effect of Clostridium difficile toxin A on human intestinal epithelial cells: induction of interleukin 8 production and apoptosis after cell detachment. Gut. 1996 Mar;38(3):337–347. doi: 10.1136/gut.38.3.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mathewson J. J., Johnson P. C., DuPont H. L., Morgan D. R., Thornton S. A., Wood L. V., Ericsson C. D. A newly recognized cause of travelers' diarrhea: enteroadherent Escherichia coli. J Infect Dis. 1985 Mar;151(3):471–475. doi: 10.1093/infdis/151.3.471. [DOI] [PubMed] [Google Scholar]
  26. Mathewson J. J., Johnson P. C., DuPont H. L., Satterwhite T. K., Winsor D. K. Pathogenicity of enteroadherent Escherichia coli in adult volunteers. J Infect Dis. 1986 Sep;154(3):524–527. doi: 10.1093/infdis/154.3.524. [DOI] [PubMed] [Google Scholar]
  27. Mathewson J. J., Oberhelman R. A., Dupont H. L., Javier de la Cabada F., Garibay E. V. Enteroadherent Escherichia coli as a cause of diarrhea among children in Mexico. J Clin Microbiol. 1987 Oct;25(10):1917–1919. doi: 10.1128/jcm.25.10.1917-1919.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Morais T. B., Gomes T. A., Sigulem D. M. Enteroaggregative Escherichia coli in infant feeding bottles. Lancet. 1997 May 17;349(9063):1448–1449. doi: 10.1016/S0140-6736(05)63724-5. [DOI] [PubMed] [Google Scholar]
  29. Nataro J. P., Deng Y., Cookson S., Cravioto A., Savarino S. J., Guers L. D., Levine M. M., Tacket C. O. Heterogeneity of enteroaggregative Escherichia coli virulence demonstrated in volunteers. J Infect Dis. 1995 Feb;171(2):465–468. doi: 10.1093/infdis/171.2.465. [DOI] [PubMed] [Google Scholar]
  30. Nataro J. P., Deng Y., Maneval D. R., German A. L., Martin W. C., Levine M. M. Aggregative adherence fimbriae I of enteroaggregative Escherichia coli mediate adherence to HEp-2 cells and hemagglutination of human erythrocytes. Infect Immun. 1992 Jun;60(6):2297–2304. doi: 10.1128/iai.60.6.2297-2304.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nataro J. P., Hicks S., Phillips A. D., Vial P. A., Sears C. L. T84 cells in culture as a model for enteroaggregative Escherichia coli pathogenesis. Infect Immun. 1996 Nov;64(11):4761–4768. doi: 10.1128/iai.64.11.4761-4768.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nataro J. P., Kaper J. B., Robins-Browne R., Prado V., Vial P., Levine M. M. Patterns of adherence of diarrheagenic Escherichia coli to HEp-2 cells. Pediatr Infect Dis J. 1987 Sep;6(9):829–831. doi: 10.1097/00006454-198709000-00008. [DOI] [PubMed] [Google Scholar]
  33. Nataro J. P., Scaletsky I. C., Kaper J. B., Levine M. M., Trabulsi L. R. Plasmid-mediated factors conferring diffuse and localized adherence of enteropathogenic Escherichia coli. Infect Immun. 1985 May;48(2):378–383. doi: 10.1128/iai.48.2.378-383.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nataro J. P., Yikang D., Yingkang D., Walker K. AggR, a transcriptional activator of aggregative adherence fimbria I expression in enteroaggregative Escherichia coli. J Bacteriol. 1994 Aug;176(15):4691–4699. doi: 10.1128/jb.176.15.4691-4699.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pai M., Kang G., Ramakrishna B. S., Venkataraman A., Muliyil J. An epidemic of diarrhoea in south India caused by enteroaggregative Escherichia coli. Indian J Med Res. 1997 Jul;106:7–12. [PubMed] [Google Scholar]
  36. Paul M., Tsukamoto T., Ghosh A. R., Bhattacharya S. K., Manna B., Chakrabarti S., Nair G. B., Sack D. A., Sen D., Takeda Y. The significance of enteroaggregative Escherichia coli in the etiology of hospitalized diarrhoea in Calcutta, India and the demonstration of a new honey-combed pattern of aggregative adherence. FEMS Microbiol Lett. 1994 Apr 15;117(3):319–325. doi: 10.1111/j.1574-6968.1994.tb06786.x. [DOI] [PubMed] [Google Scholar]
  37. Rocha M. F., Maia M. E., Bezerra L. R., Lyerly D. M., Guerrant R. L., Ribeiro R. A., Lima A. A. Clostridium difficile toxin A induces the release of neutrophil chemotactic factors from rat peritoneal macrophages: role of interleukin-1beta, tumor necrosis factor alpha, and leukotrienes. Infect Immun. 1997 Jul;65(7):2740–2746. doi: 10.1128/iai.65.7.2740-2746.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Savarino S. J., Fasano A., Robertson D. C., Levine M. M. Enteroaggregative Escherichia coli elaborate a heat-stable enterotoxin demonstrable in an in vitro rabbit intestinal model. J Clin Invest. 1991 Apr;87(4):1450–1455. doi: 10.1172/JCI115151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Savarino S. J., Fasano A., Watson J., Martin B. M., Levine M. M., Guandalini S., Guerry P. Enteroaggregative Escherichia coli heat-stable enterotoxin 1 represents another subfamily of E. coli heat-stable toxin. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):3093–3097. doi: 10.1073/pnas.90.7.3093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Savarino S. J., Fox P., Deng Y., Nataro J. P. Identification and characterization of a gene cluster mediating enteroaggregative Escherichia coli aggregative adherence fimbria I biogenesis. J Bacteriol. 1994 Aug;176(16):4949–4957. doi: 10.1128/jb.176.16.4949-4957.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Savarino S. J., McVeigh A., Watson J., Cravioto A., Molina J., Echeverria P., Bhan M. K., Levine M. M., Fasano A. Enteroaggregative Escherichia coli heat-stable enterotoxin is not restricted to enteroaggregative E. coli. J Infect Dis. 1996 Apr;173(4):1019–1022. doi: 10.1093/infdis/173.4.1019. [DOI] [PubMed] [Google Scholar]
  42. Scaletsky I. C., Silva M. L., Trabulsi L. R. Distinctive patterns of adherence of enteropathogenic Escherichia coli to HeLa cells. Infect Immun. 1984 Aug;45(2):534–536. doi: 10.1128/iai.45.2.534-536.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Schmidt H., Knop C., Franke S., Aleksic S., Heesemann J., Karch H. Development of PCR for screening of enteroaggregative Escherichia coli. J Clin Microbiol. 1995 Mar;33(3):701–705. doi: 10.1128/jcm.33.3.701-705.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schorling J. B., McAuliffe J. F., de Souza M. A., Guerrant R. L. Malnutrition is associated with increased diarrhoea incidence and duration among children in an urban Brazilian slum. Int J Epidemiol. 1990 Sep;19(3):728–735. doi: 10.1093/ije/19.3.728. [DOI] [PubMed] [Google Scholar]
  45. Smith H. R., Cheasty T., Rowe B. Enteroaggregative Escherichia coll and outbreaks of gastroenteritis in UK. Lancet. 1997 Sep 13;350(9080):814–815. doi: 10.1016/s0140-6736(05)62611-6. [DOI] [PubMed] [Google Scholar]
  46. Smith H. R., Scotland S. M., Willshaw G. A., Rowe B., Cravioto A., Eslava C. Isolates of Escherichia coli O44:H18 of diverse origin are enteroaggregative. J Infect Dis. 1994 Dec;170(6):1610–1613. doi: 10.1093/infdis/170.6.1610. [DOI] [PubMed] [Google Scholar]
  47. Steiner T. S., Lima A. A., Nataro J. P., Guerrant R. L. Enteroaggregative Escherichia coli produce intestinal inflammation and growth impairment and cause interleukin-8 release from intestinal epithelial cells. J Infect Dis. 1998 Jan;177(1):88–96. doi: 10.1086/513809. [DOI] [PubMed] [Google Scholar]
  48. Tzipori S., Montanaro J., Robins-Browne R. M., Vial P., Gibson R., Levine M. M. Studies with enteroaggregative Escherichia coli in the gnotobiotic piglet gastroenteritis model. Infect Immun. 1992 Dec;60(12):5302–5306. doi: 10.1128/iai.60.12.5302-5306.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Vial P. A., Mathewson J. J., DuPont H. L., Guers L., Levine M. M. Comparison of two assay methods for patterns of adherence to HEp-2 cells of Escherichia coli from patients with diarrhea. J Clin Microbiol. 1990 May;28(5):882–885. doi: 10.1128/jcm.28.5.882-885.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Vial P. A., Robins-Browne R., Lior H., Prado V., Kaper J. B., Nataro J. P., Maneval D., Elsayed A., Levine M. M. Characterization of enteroadherent-aggregative Escherichia coli, a putative agent of diarrheal disease. J Infect Dis. 1988 Jul;158(1):70–79. doi: 10.1093/infdis/158.1.70. [DOI] [PubMed] [Google Scholar]
  51. Wai S. N., Takade A., Amako K. The hydrophobic surface protein layer of enteroaggregative Escherichia coli strains. FEMS Microbiol Lett. 1996 Jan 1;135(1):17–22. doi: 10.1111/j.1574-6968.1996.tb07960.x. [DOI] [PubMed] [Google Scholar]
  52. Wanke C. A., Cronan S., Goss C., Chadee K., Guerrant R. L. Characterization of binding of Escherichia coli strains which are enteropathogens to small-bowel mucin. Infect Immun. 1990 Mar;58(3):794–800. doi: 10.1128/iai.58.3.794-800.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Wanke C. A., Schorling J. B., Barrett L. J., Desouza M. A., Guerrant R. L. Potential role of adherence traits of Escherichia coli in persistent diarrhea in an urban Brazilian slum. Pediatr Infect Dis J. 1991 Oct;10(10):746–751. doi: 10.1097/00006454-199110000-00006. [DOI] [PubMed] [Google Scholar]
  54. Yamamoto T., Echeverria P., Yokota T. Drug resistance and adherence to human intestines of enteroaggregative Escherichia coli. J Infect Dis. 1992 Apr;165(4):744–749. doi: 10.1093/infdis/165.4.744. [DOI] [PubMed] [Google Scholar]

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