Volume 96, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Enterotoxigenic (ETEC) can be attributed to around 200 million diarrheal episodes and 380,000 deaths in the developing regions. Travelers' diarrhea occurs in 15–40% of travelers to developing regions with ETEC being the most important etiologic agent. This study aims to describe the distribution of enterotoxins and colonization factor (CF) profiles of ETEC isolates from stool samples of adult travelers acquiring diarrhea in Mexico, Guatemala, and India and a group of children with acute diarrhea in Houston, TX, between 2007 and 2012. The heat-labile/heat-stable (LT/ST) enterotoxins and CFs from 252 patients were determined using polymerase chain reaction assay. Among the 252 ETEC isolates, 15% were LT-only, 58% were ST-only, and 28% produced both LT and ST. The distribution of LT-only (12–15%) and ST-only (55–56%) isolates was similar between Latin American and Indian sites. The most prevalent CF was CS21, expressed in 65% of the isolates followed by CS6 (25%) and CS3 (17%). Among the international travelers, 64% of the ETEC isolates expressed CS21. CS21 was expressed in 46% of isolates from Latin America compared with 96% of isolates from India ( < 0.0001). CS21 was expressed in 85% isolates from Houston children. CS21 was increasingly found in ST-only ( = 0.003) and ST/LT ( = 0.026) ETEC compared with LT-only ETEC. High frequency of finding CS21 among recent isolates of ETEC over a wide geographic distribution warrants additional studies on this CF. Highly conserved CS21 is an important target for potential multivalent ETEC vaccines.


Article metrics loading...

Loading full text...

Full text loading...



  1. Steffen R, Hill DR, DuPont HL, , 2015. Traveler's diarrhea: a clinical review. JAMA 313: 7180.[Crossref]
  2. Diarrheal Diseases, 2015. WHO Media Center, 2013. Available at: http://www.who.int/mediacentre/factsheets/fs369/en/. Accessed October 13, 2016.
  3. Wenneras C, Erling V, , 2004. Prevalence of enterotoxigenic Escherichia coli-associated diarrhoea and carrier state in the developing world. J Health Popul Nutr 22: 370382.
  4. Steffen R, Castelli F, Dieter Nothdurft H, Rombo L, Jane Zuckerman N, , 2005. Vaccination against enterotoxigenic Escherichia coli, a cause of travelers' diarrhea. J Travel Med 12: 102107.[Crossref]
  5. Shah N, DuPont HL, Ramsey DJ, , 2009. Global etiology of travelers' diarrhea: systematic review from 1973 to the present. Am J Trop Med Hyg 80: 609614.
  6. Isidean SD, Riddle MS, Savarino SJ, Porter CK, , 2011. A systematic review of ETEC epidemiology focusing on colonization factor and toxin expression. Vaccine 29: 61676178.[Crossref]
  7. Freedman DJ, Tacket CO, Delehanty A, Maneval DR, Nataro J, Crabb JH, , 1998. Milk immunoglobulin with specific activity against purified colonization factor antigens can protect against oral challenge with enterotoxigenic Escherichia coli . J Infect Dis 177: 662667.[Crossref]
  8. Rudin A, Olbe L, Svennerholm AM, , 1996. Monoclonal antibodies against fimbrial subunits of colonization factor antigen I (CFA/I) inhibit binding to human enterocytes and protect against enterotoxigenic Escherichia coli expressing heterologous colonization factors. Microb Pathog 21: 3545.[Crossref]
  9. Tacket CO, Losonsky G, Link H, Hoang Y, Guesry P, Hilpert H, Levine MM, , 1998. Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli . N Engl J Med 318: 12401243.[Crossref]
  10. Ahren CM, Svennerholm AM, , 1982. Synergistic protective effect of antibodies against Escherichia coli enterotoxin and colonization factor antigens. Infect Immun 38: 7479.
  11. Svennerholm AM, Tobias J, , 2008. Vaccines against enterotoxigenic Escherichia coli . Expert Rev Vaccines 7: 795804.[Crossref]
  12. Qadri F, Svennerholm AM, Faruque AS, Sack RB, , 2005. Enterotoxigenic Escherichia coli in developing countries: epidemiology, microbiology, clinical features, treatment, and prevention. Clin Microbiol Rev 18: 465483.[Crossref]
  13. Harro C, Sack D, Bourgeois AL, Walker R, DeNearing B, Feller A, Chakraborty S, Buchwaldt C, Darsley MJ, , 2011. A combination vaccine consisting of three live attenuated enterotoxigenic Escherichia coli strains expressing a range of colonization factors and heat-labile toxin subunit B is well tolerated and immunogenic in a placebo-controlled double-blind phase I trial in healthy adults. Clin Vaccine Immunol 18: 21182127.[Crossref]
  14. Torres OR, Gonzalez W, Lemus O, Pratdesaba RA, Matute JA, Wiklund G, Sack DA, Bourgeois AL, Svennerholm AM, , 2015. Toxins and virulence factors of enterotoxigenic Escherichia coli associated with strains isolated from indigenous children and international visitors to a rural community in Guatemala. Epidemiol Infect 143: 16621671.[Crossref]
  15. Jiang ZD, Lowe B, Verenkar MP, Ashley D, Steffen R, Tornieporth N, von Sonnenburg F, Waiyaki P, DuPont HL, , 2002. Prevalence of enteric pathogens among international travelers with diarrhea acquired in Kenya (Mombasa), India (Goa), or Jamaica (Montego Bay). J Infect Dis 185: 497502.[Crossref]
  16. API, 2015. Be the First to Know. Available at: http://www.biomerieux-usa.com/clinical/api. Accessed October 13, 2016.
  17. Rodas C, Iniguez V, Qadri F, Wiklund G, Svennerholm AM, Sjoling A, , 2009. Development of multiplex PCR assays for detection of enterotoxigenic Escherichia coli colonization factors and toxins. J Clin Microbiol 47: 12181220.[Crossref]
  18. Sjoling A, Wiklund G, Savarino SJ, Cohen DI, Svennerholm AM, , 2007. Comparative analyses of phenotypic and genotypic methods for detection of enterotoxigenic Escherichia coli toxins and colonization factors. J Clin Microbiol 45: 32953301.[Crossref]
  19. Zhang C, Knudsen DE, Liu M, Robertson DC, Zhang W, STa Toxoid Vaccine Consortium Group; , 2013. Toxicity and immunogenicity of enterotoxigenic Escherichia coli heat-labile and heat-stable toxoid fusion in a murine model. PLoS One 8: e77386.[Crossref]
  20. Taxt A, Aasland R, Sommerfelt H, Nataro J, Puntervoll P, , 2010. Heat-stable enterotoxin of enterotoxigenic Escherichia coli as a vaccine target. Infect Immun 78: 18241831.[Crossref]
  21. Frech SA, Dupont HL, Bourgeois AL, McKenzie R, Belkind-Gerson J, Figueroa JF, Okhuysen PC, Guerrero NH, Martinez-Sandoval FG, Meléndez-Romero JH, Jiang ZD, Asturias EJ, Halpern J, Torres OR, Hoffman AS, Villar CP, Kassem RN, Flyer DC, Andersen BH, Kazempour K, Breisch SA, Glenn GM, , 2008. Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled field trial. Lancet 371: 20192025.[Crossref]
  22. Sack DA, Shimko J, Torres O, Bourgeois AL, Francia DS, Gustafsson B, Kärnell A, Nyquist I, Svennerholm AM, , 2007. Randomised, double-blind, safety and efficacy of a killed oral vaccine for enterotoxigenic E. coli diarrhoea of travellers to Guatemala and Mexico. Vaccine 25: 43924400.[Crossref]
  23. Guerra JA, Romero-Herazo YC, Arzuza O, Gomez-Duarte OG, , 2014. Phenotypic and genotypic characterization of enterotoxigenic Escherichia coli clinical isolates from northern Colombia, South America. Biomed Res Int 2014: 236260.[Crossref]
  24. Clavijo AP, Bai J, Gomez-Duarte OG, , 2010. The Longus type IV pilus of enterotoxigenic Escherichia coli (ETEC) mediates bacterial self-aggregation and protection from antimicrobial agents. Microb Pathog 48: 230238.[Crossref]
  25. Guevara CP, Luiz WB, Sierra A, Cruz C, Qadri F, Kaushik RS, Ferreira LC, Gómez-Duarte OG, , 2013. Enterotoxigenic Escherichia coli CS21 pilus contributes to adhesion to intestinal cells and to pathogenesis under in vivo conditions. Microbiol 159: 17251735.[Crossref]
  26. Cruz-Cordova A, Espinosa-Mazariego K, Ochoa SA, Saldaña Z, Rodea GE, Cázares-Domínguez V, Rodríguez-Ramírez V, Eslava-Campos CA, Navarro-Ocaña A, Arrellano-Galindo J, Hernández-Castro R, Gómez-Duarte OG, Qadri F, Xicohtencatl-Cortes J, , 2014. CS21 positive multidrug-resistant ETEC clinical isolates from children with diarrhea are associated with self-aggregation, and adherence. Front Microbiol 5: 709.
  27. Chatterjee R, Ghosal A, Sabui S, Chatterjee NS, , 2011. Three dimensional modeling of C-terminal loop of CssA subunit in CS6 of enterotoxigenic Escherichia coli and its interaction with the 70 KDa domain of Fibronectin. Bioinformation 6: 307310.[Crossref]
  28. Debnath A, Wajima T, Sabui S, Hamabata T, Ramamurthy T, Chatterjee NS, , 2015. Two specific amino acid variations in colonization factor CS6 subtypes of enterotoxigenic Escherichia coli results in differential binding and pathogenicity. Microbiology 161: 865874.[Crossref]
  29. Rao MR, Wierzba TF, Savarino SJ, Abu-Elyazeed R, El-Ghoreb N, Hall ER, Naficy A, Abdel-Messih I, Frenck RW, Jr Svennerholm AM, Clemens JD, , 2005. Serologic correlates of protection against enterotoxigenic Escherichia coli diarrhea. J Infect Dis 191: 562570.[Crossref]
  30. Nicklasson M, Sjoling A, von Mentzer A, Qadri F, Svennerholm AM, , 2012. Expression of colonization factor CS5 of enterotoxigenic Escherichia coli (ETEC) is enhanced in vivo and by the bile component Na glycocholate hydrate. PLoS One 7: e35827.[Crossref]
  31. Rivera FP, Medina AM, Aldasoro E, Gascon J, Ochoa TJ, Vila J, Ruiz J, , 2013. Genotypic characterization of enterotoxigenic Escherichia coli strains causing traveler's diarrhea. J Clin Microbiol 51: 633635.[Crossref]
  32. Holmgren J, Bourgeois L, Carlin N, Clements J, Gustafsson B, Lundgren A, Nygren E, Tobias J, Walker R, Svennerholm AM, , 2013. Development and preclinical evaluation of safety and immunogenicity of an oral ETEC vaccine containing inactivated E. coli bacteria overexpressing colonization factors CFA/I, CS3, CS5 and CS6 combined with a hybrid LT/CT B subunit antigen, administered alone and together with dmLT adjuvant. Vaccine 31: 24572464.[Crossref]
  33. Bourgeois AL, Wierzba TF, Walker RI, , 2016. Status of vaccine research and development for enterotoxigenic Escherichia coli . Vaccine 34: 28802886.[Crossref]
  34. Darsley MJ, Chakraborty S, DeNearing B, Sack DA, Feller A, Buchwaldt C, Bourgeois AL, Walker R, Harro CD, , 2012. The oral, live attenuated enterotoxigenic Escherichia coli vaccine ACE527 reduces the incidence and severity of diarrhea in a human challenge model of diarrheal disease. Clin Vaccine Immunol 19: 19211931.[Crossref]
  35. Rivera FP, Medina AM, Aldasoro E, Sangil A, Gascon J, Ochoa TJ, Vila J, Ruiz J, , 2013. Genotypic characterization of enterotoxigenic Escherichia coli strains causing traveler's diarrhea. J Clin Microbiol 51: 633635.[Crossref]

Data & Media loading...

  • Received : 19 May 2016
  • Accepted : 23 Aug 2016

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error