Skip to main content

Escherichia coli STb Enterotoxin: A Multifaceted Molecule

  • Living reference work entry
  • First Online:
Microbial Toxins

Part of the book series: Toxinology ((TOXI))

  • 432 Accesses

Abstract

Enterotoxigenic Escherichia coli (ETEC) produce heat-labile and heat-stable toxins. These toxins are active on the epithelial cells of the small intestine of man and animals affecting the fluid homeostasis. One of the heat-stable toxins enterotoxin b (STb) is responsible for secretory diarrhea in animals and more specifically in pigs. Recent studies have provided information on the nature of its receptor and the structure-function of the toxin. The toxin was shown to form oligomers and this process seems indispensable for toxicity expression. As observed with in vitro models and cells in culture, diverse activities were determined for STb and some or all of these may account for the secretion resulting from the activity of this toxin. The next step will be to determine quantitatively how important each of these activities is on fluid secretion. The relative importance of STb compared to other ETEC toxins has been clarified in recent years. As STb is now recognized as a major player in post-weaning diarrhea in pigs, the focus has been on ways to prevent its toxicity. For example, vaccines composed of multivalent toxin molecules were designed, and preliminary results indicate that it could represent a reliable way to protect from ETEC intoxication. As described for many other bacterial toxins, in the near future, STb could be utilized as a tool to decipher cellular physiological process.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

Similar content being viewed by others

References

  • Beausoleil HE, Lepine F, Dubreuil JD. LC-MS analysis of pig intestine sulfatides: interaction with Escherichia coli STb enterotoxin and characterization of molecular species present. FEMS Microbiol Lett. 2002;209:183–8.

    Article  CAS  PubMed  Google Scholar 

  • Berberov EM, Zhou Y, Francis DH, Scott MA, Kachman SD, Moxley RA. Relative importance of heat-labile enterotoxin in the causation of severe diarrheal disease in the gnotobiotic piglet model by a strain of enterotoxigenic Escherichia coli that produces multiple enterotoxins. Infect Immun. 2004;72:3914–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burgess MN, Bywater RJ, Cowley CM, Mullan NA, Newsome PM. Biological evaluation of a methanol-soluble, heat-stable Escherichia coli enterotoxin in infant mice, pigs, rabbits, and calves. Infect Immun. 1978;21:526–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Busque P, Letellier A, Harel J, Dubreuil JD. Production of Escherichia coli STb enterotoxin is subject to catabolite repression. Microbiology. 1995;141:1621–7.

    Article  CAS  PubMed  Google Scholar 

  • Chapman TA, Wu XY, Barchia I, Bettelheim KA, Driesen S, Trott D, Wilson M, Chin JJ. Comparison of virulence gene profiles of Escherichia coli strains isolated from healthy and diarrheic swine. Appl Environ Microbiol. 2006;72:4782–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen X, Huan H, Wan T, Wang L, Gao S, Jiao X. Antigenic determinants analysis and detection of virulence factors in F18 fimbriae Escherichia coli strains isolated from pigs. Wei Sheng Wu Xue Bao. 2014;54:236–42.

    CAS  PubMed  Google Scholar 

  • Cox E, Van der Stede Y, Verdonck F, Snoeck V, Van den Broeck W, Goddeeris B. Oral immunisation of pigs with fimbrial antigens of enterotoxigenic E. coli: an interesting model to study mucosal immune mechanisms. Vet Immunol Immunopathol. 2002;87:287–90.

    Article  CAS  PubMed  Google Scholar 

  • Dreyfus LA, Harville B, Howard DE, Shaban R, Beatty DM, Morris SJ. Calcium influx mediated by the Escherichia coli heat-stable enterotoxin B (STB). Proc Natl Acad Sci USA. 1993;90:3202–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dubreuil JD. Escherichia coli STb toxin and prostaglandin production. Microbiology. 1999;145:1507–8.

    Article  CAS  PubMed  Google Scholar 

  • Dubreuil JD. Escherichia coli STb toxin and colibacillosis: knowing is half the battle. FEMS Microbiol Lett. 2008;278:137–45.

    Article  CAS  PubMed  Google Scholar 

  • Dubreuil JD. The whole Shebang: the gastrointestinal tract, Escherichia coli enterotoxins and secretion. Curr Issues Mol Biol. 2012;14:71–82.

    PubMed  Google Scholar 

  • Erume J, Berberov EM, Moxley RA. Comparison of the effects of different nutrient media on production of heat-stable enterotoxin-b by Escherichia coli. Vet Microbiol. 2010;144:160–5.

    Article  CAS  PubMed  Google Scholar 

  • Erume J, Wijemanne P, Berberov EM, Kachman SD, Oestmann DJ, Francis DH, Moxley RA. Inverse relationship between heat stable enterotoxin-b induced fluid accumulation and adherence of F4ac-positive enterotoxigenic Escherichia coli in ligated jejunal loops of F4ab/ac fimbria receptor-positive swine. Vet Microbiol. 2013;161:315–24.

    Article  CAS  PubMed  Google Scholar 

  • Fairbrother JM, Nadeau E, Gyles CL. Escherichia coli in postweaning diarrhea in pigs: an update on bacterial types, pathogenesis, and prevention strategies. Anim Health Res Rev. 2005;6:17–39.

    Article  CAS  PubMed  Google Scholar 

  • Fujii Y, Kondo Y, Okamoto K. Involvement of prostaglandin E2 synthesis in the intestinal secretory action of Escherichia coli heat-stable enterotoxin II. FEMS Microbiol Lett. 1995;130:259–65.

    Article  CAS  PubMed  Google Scholar 

  • Fujii Y, Nomura T, Yamanaka H, Okamoto K. Involvement of Ca(2+)-calmodulin-dependent protein kinase II in the intestinal secretory action of Escherichia coli heat-stable enterotoxin II. Microbiol Immunol. 1997;41:633–6.

    Article  CAS  PubMed  Google Scholar 

  • Goncalves C, Dubreuil JD. Effect of Escherichia coli STb toxin on NIH-3T3 cells. FEMS Immunol Med Microbiol. 2009;55:432–41.

    Article  CAS  PubMed  Google Scholar 

  • Goncalves C, Vachon V, Schwartz JL, Dubreuil JD. The Escherichia coli enterotoxin STb permeabilizes piglet jejunal brush border membrane vesicles. Infect Immun. 2007;75:2208–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goncalves C, Berthiaume F, Mourez M, Dubreuil JD. Escherichia coli STb toxin binding to sulfatide and its inhibition by carragenan. FEMS Microbiol Lett. 2008;281:30–5.

    Article  CAS  PubMed  Google Scholar 

  • Guttman JA, Finlay BB. Subcellular alterations that lead to diarrhea during bacterial pathogenesis. Trends Microbiol. 2008;16:535–42.

    Article  CAS  PubMed  Google Scholar 

  • Handl CE, Flock JI. STb producing Escherichia coli are rarely associated with infantile diarrhoea. J Diarrhoeal Dis Res. 1992;10:37–8.

    CAS  PubMed  Google Scholar 

  • Harville BA, Dreyfus LA. Involvement of 5-hydroxytryptamine and prostaglandin E2 in the intestinal secretory action of Escherichia coli heat-stable enterotoxin B. Infect Immun. 1995;63:745–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hitotsubashi S, Akagi M, Saitou A, Yamanaka H, Fujii Y, Okamoto K. Action of Escherichia coli heat-stable enterotoxin II on isolated sections of mouse ileum. FEMS Microbiol Lett. 1992a;69:249–52.

    Article  CAS  PubMed  Google Scholar 

  • Hitotsubashi S, Fujii Y, Yamanaka H, Okamoto K. Some properties of purified Escherichia coli heat-stable enterotoxin II. Infect Immun. 1992b;60:4468–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Labrie V, Beausoleil HE, Harel J, Dubreuil JD. Binding to sulfatide and enterotoxicity of various Escherichia coli STb mutants. Microbiology. 2001a;147:3141–8.

    Article  CAS  PubMed  Google Scholar 

  • Labrie V, Harel J, Dubreuil JD. Oligomerization of Escherichia coli enterotoxin b through its C-terminal hydrophobic alpha-helix. Biochim Biophys Acta. 2001b;1535:128–33.

    Article  CAS  PubMed  Google Scholar 

  • Labrie V, Harel J, Dubreuil JD. Escherichia coli heat-stable enterotoxin b (STb) in vivo internalization within rat intestinal epithelial cells. Vet Res. 2002;33:223–8.

    Article  PubMed  Google Scholar 

  • Liu W, Yuan C, Meng X, Du Y, Gao R, Tang J, Shi D. Frequency of virulence factors in Escherichia coli isolated from suckling pigs with diarrhoea in China. Vet J. 2014;199:286–9.

    Article  PubMed  Google Scholar 

  • Liu W, Li J, Bao J, Li X, Guan W, Yuan C, Tang J, Zhao Z, Shi D. Simultaneous oral immunization of mice with live attenuated Escherichia coli expressing LT192-STa 13 and LT 192-STb fusion immunogen, respectively, for polyvalent vaccine candidate. Appl Microbiol Biotechnol. 2015;99:3981–92.

    Article  CAS  PubMed  Google Scholar 

  • Loos M, Geens M, Schauvliege S, Gasthuys F, van der Meulen J, Dubreuil JD, Goddeeris BM, Niewold T, Cox E. Role of heat-stable enterotoxins in the induction of early immune responses in piglets after infection with enterotoxigenic Escherichia coli. PLoS One. 2012;7:e41041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lortie LA, Dubreuil JD, Harel J. Characterization of Escherichia coli strains producing heat-stable enterotoxin b (STb) isolated from humans with diarrhea. J Clin Microbiol. 1991;29:656–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lucas ML. Diarrhoeal disease through enterocyte secretion: a doctrine untroubled by proof. Exp Physiol. 2010;95:479–84.

    Article  PubMed  Google Scholar 

  • Lucas ML, Thom MM, Bradley JM, O'Reilly NF, McIlvenny TJ, Nelson YB. Escherichia coli heat stable (STa) enterotoxin and the upper small intestine: lack of evidence in vivo for net fluid secretion. J Membr Biol. 2005;206:29–42.

    Article  CAS  PubMed  Google Scholar 

  • Melkebeek V, Goddeeris BM, Cox E. ETEC vaccination in pigs. Vet Immunol Immunopathol. 2013;152:37–42.

    Article  CAS  PubMed  Google Scholar 

  • Menard LP, Dubreuil JD. Enteroaggregative Escherichia coli heat-stable enterotoxin 1 (EAST1): a new toxin with an old twist. Crit Rev Microbiol. 2002;28:43–60.

    Article  CAS  PubMed  Google Scholar 

  • Mohlatlole RP, Madoroba E, Muchadeyi FC, Chimonyo M, Kanengoni AT, Dzomba EF. Virulence profiles of enterotoxigenic, shiga toxin and enteroaggregative Escherichia coli in South African pigs. Trop Anim Health Prod. 2013;45:1399–405.

    Article  PubMed  Google Scholar 

  • Moon HW, Schneider RA, Moseley SL. Comparative prevalence of four enterotoxin genes among Escherichia coli isolated from swine. Am J Vet Res. 1986;47:210–2.

    CAS  PubMed  Google Scholar 

  • Moredo FA, Pineyro PE, Marquez GC, Sanz M, Colello R, Etcheverria A, Padola NL, Quiroga MA, Perfumo CJ, Galli L, Leotta GA. Enterotoxigenic Escherichia coli subclinical infection in pigs: bacteriological and genotypic characterization and antimicrobial resistance profiles. Foodborne Pathog Dis. 2015;12:704–11.

    Article  CAS  PubMed  Google Scholar 

  • Nagy B, Fekete PZ. Enterotoxigenic Escherichia coli in veterinary medicine. Int J Med Microbiol. 2005;295:443–54.

    Article  CAS  PubMed  Google Scholar 

  • Nassour H, Dubreuil JD. Escherichia coli STb enterotoxin dislodges claudin-1 from epithelial tight junctions. PLoS One. 2014;9:e113273.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ngendahayo Mukiza C, Dubreuil JD. Escherichia coli heat-stable toxin b impairs intestinal epithelial barrier function by altering tight junction proteins. Infect Immun. 2013;81:2819–27.

    Article  PubMed  PubMed Central  Google Scholar 

  • Okamoto K, Fujii Y, Akashi N, Hitotsubashi S, Kurazono H, Karasawa T, Takeda Y. Identification and characterization of heat-stable enterotoxin II-producing Escherichia coli from patients with diarrhea. Microbiol Immunol. 1993;37:411–4.

    Article  CAS  PubMed  Google Scholar 

  • Peterson JW, Whipp SC. Comparison of the mechanisms of action of cholera toxin and the heat-stable enterotoxins of Escherichia coli. Infect Immun. 1995;63:1452–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rousset E, Harel J, Dubreuil JD. Sulfatide from the pig jejunum brush border epithelial cell surface is involved in binding of Escherichia coli enterotoxin b. Infect Immun. 1998;66:5650–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Santiago-Mateo K, Zhao M, Lin J, Zhang W, Francis DH. Avirulent K88 (F4)+ Escherichia coli strains constructed to express modified enterotoxins protect young piglets from challenge with a virulent enterotoxigenic Escherichia coli strain that expresses the same adhesion and enterotoxins. Vet Microbiol. 2012;159:337–42.

    CAS  PubMed  Google Scholar 

  • Schmidt E, Kelly SM, van der Walle CF. Tight junction modulation and biochemical characterisation of the zonula occludens toxin C-and N-termini. FEBS Lett. 2007;581:2974–80.

    Article  CAS  PubMed  Google Scholar 

  • Sukumar M, Rizo J, Wall M, Dreyfus LA, Kupersztoch YM, Gierasch LM. The structure of Escherichia coli heat-stable enterotoxin b by nuclear magnetic resonance and circular dichroism. Protein Sci. 1995;4:1718–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Syed HC, Dubreuil JD. Escherichia coli STb toxin induces apoptosis in intestinal epithelial cell lines. Microb Pathog. 2012;53:147–53.

    Article  CAS  PubMed  Google Scholar 

  • Taillon C, Nadeau E, Mourez M, Dubreuil JD. Heterogeneity of Escherichia coli STb enterotoxin isolated from diseased pigs. J Med Microbiol. 2008;57:887–90.

    Article  CAS  PubMed  Google Scholar 

  • Taillon C, Hancock MA, Mourez M, Dubreuil JD. Biochemical and biological characterization of Escherichia coli STb His12 to Asn variant. Toxicon. 2012;59:300–5.

    Article  CAS  PubMed  Google Scholar 

  • Taxt A, Aasland R, Sommerfelt H, Nataro J, Puntervoll P. Heat-stable enterotoxin of enterotoxigenic Escherichia coli as a vaccine target. Infect Immun. 2010;78:1824–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vidotto MC, de Lima NC, Fritzen JT, de Freitas JC, Venancio MJ, Ono MA. Frequency of virulence genes in Escherichia coli strains isolated from piglets with diarrhea in the North Parana State, Brazil. Braz J Microbiol. 2009;40:199–204.

    Article  PubMed  PubMed Central  Google Scholar 

  • Whipp SC, Moon HW, Kemeny LJ, Argenzio RA. Effect of virus-induced destruction of villous epithelium on intestinal secretion induced by heat-stable Escherichia coli enterotoxins and prostaglandin E1 in swine. Am J Vet Res. 1985;46:637–42.

    CAS  PubMed  Google Scholar 

  • Whipp SC, Moseley SL, Moon HW. Microscopic alterations in jejunal epithelium of 3-week-old pigs induced by pig-specific, mouse-negative, heat-stable Escherichia coli enterotoxin. Am J Vet Res. 1986;47:615–8.

    CAS  PubMed  Google Scholar 

  • You J, Xu Y, He M, McAllister TA, Thacker PA, Li X, Wang T, Jin L. Protection of mice against enterotoxigenic E. coli by immunization with a polyvalent enterotoxin comprising a combination of LTB, STa, and STb. Appl Microbiol Biotechnol. 2011;89:1885–93.

    Article  CAS  PubMed  Google Scholar 

  • You J, Xu Y, Li H, Wang L, Wu F, Xu F, Jin L, Li S, Li X. Chicken egg yolk immunoglobulin (IgY) developed against fusion protein LTB-STa-STb neutralizes the toxicity of Escherichia coli heat-stable enterotoxins. J Appl Microbiol. 2014;117:320–8.

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Francis DH. Genetic fusions of heat-labile toxoid (LT) and heat-stable toxin b (STb) of porcine enterotoxigenic Escherichia coli elicit protective anti-LT and anti-STb antibodies. Clin Vaccine Immunol. 2010;17:1223–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Sack DA. Current progress in developing subunit vaccines against enterotoxigenic Escherichia coli-associated diarrhea. Clin Vaccine Immunol. 2015;22:983–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Berberov EM, Freeling J, He D, Moxley RA, Francis DH. Significance of heat-stable and heat-labile enterotoxins in porcine colibacillosis in an additive model for pathogenicity studies. Infect Immun. 2006;74:3107–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

J.D.D. is the recipient of a Discovery Grant from the National Sciences and Engineering Research Council of Canada (139070). The author thanks Mrs. Jacinthe Lachance for the artwork.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Daniel Dubreuil .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Dubreuil, J.D. (2016). Escherichia coli STb Enterotoxin: A Multifaceted Molecule. In: Gopalakrishnakone, P., Stiles, B., Alape-Girón, A., Dubreuil, J., Mandal, M. (eds) Microbial Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6725-6_21-1

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-6725-6_21-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-6725-6

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics