Non-pathogenic Escherichia coli (Ec) strains K12 (EcK12) and Nissle 1917 (EcN) are used for gene technology and probiotic treatment of intestinal inflammation, respectively. We investigated intestinal colonization and potential pro-inflammatory properties of EcK12, EcN, and commensal E. coli (EcCo) strains in Toxoplasma (T.) gondii-induced acute ileitis. Whereas gnotobiotic animals generated by quintuple antibiotic treatment were protected from ileitis, mice replenished with conventional microbiota suffered from small intestinal necrosis 7 days post-T. gondii infection (p.i.). Irrespective of the Ec strain, recolonized mice revealed mild to moderate histopathological changes in their ileal mucosa. Upon stable recolonization with EcK12, EcN, or EcCo, development of inflammation was accompanied by pro-inflammatory responses at day 7 p.i., including increased ileal T lymphocyte and apoptotic cell numbers compared to T. gondii-infected gnotobiotic controls. Strikingly, either Ec strain was capable to translocate to extraintestinal locations, such as MLN, spleen, and liver. Taken together, Ec strains used in gene technology and probiotic treatment are able to exert inflammatory responses in a murine model of small intestinal inflammation. In conclusion, the therapeutic use of Ec strains in patients with broad-spectrum antibiotic treatment and/or intestinal inflammation should be considered with caution.
1. H.W. Smith 1978 Is it safe to use Escherichia coli K 12 in recombinant DNA experiments? J Infect Dis 137 655 660.
2. R. Curtiss 3rd 1978 Biological containment and cloning vector transmissibility J Infect Dis 137 668 675.
3. J. Lederberg E.L. Tatum 1946 Gene recombination in Escherichia coli Nature 158 558.
4. H.W. Smith 1975 Survival of orally administered E. coli K 12 in alimentary tract of man Nature 255 500 502.
5. A.K. Moller M.P. Leatham T. Conway P.J. Nuijten L.A. de Haan et al.2003 An Escherichia coli MG1655 lipopolysaccharide deep-rough core mutant grows and survives in mouse cecal mucus but fails to colonize the mouse large intestine Infect Immun 71 2142 2152.
6. Hayashi K , Morooka N, Yamamoto Y, Fujita K, Isono K et al.: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol 2006. 0007 (2006).
7. R. Lodinova-Zadnikova U. Sonnenborn 1997 Effect of preventive administration of a nonpathogenic Escherichia coli strain on the colonization of the intestine with microbial pathogens in newborn infants Biol Neonate 71 224 232.
8. F. Shanahan 2000 Probiotics and inflammatory bowel disease: is there a scientific rationale? Inflamm Bowel Dis 6 107 115.
9. F. Shanahan 2001 Probiotics in inflammatory bowel disease Gut 48 609.
10. A. Nissle 1918 Die antagonistische Behandlung chronischer Darmstörungen mit Colibekaterien Med Klin 2 29 30.
11. G. Blum R. Marre J. Hacker 1995 Properties of Escherichia coli strains of serotype O6 Infection 23 234 236.
12. J. Henker M. Laass B.M. Blokhin Y.K. Bolbot V.G. Maydannik et al.2007 The probiotic Escherichia coli strain Nissle 1917 (EcN) stops acute diarrhoea in infants and toddlers Eur J Pediatr 166 311 318.
13. W. Kruis P. Fric J. Pokrotnieks M. Lukas B. Fixa et al.2004 Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine Gut 53 1617 1623.
14. S. Fujimori A. Tatsuguchi K. Gudis T. Kishida K. Mitsui et al.2007 High dose probiotic and prebiotic cotherapy for remission induction of active Crohn's disease J Gastroenterol Hepatol 22 1199 1204.
15. O. Liesenfeld J. Kosek J.S. Remington Y. Suzuki 1996 Association of CD4+ T cell-dependent, interferon-gamma-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii J Exp Med 184 597 607.
16. O. Liesenfeld 2002 Oral infection of C 57BL/6 mice with Toxoplasma gondii: a new model of inflammatory bowel disease? J Infect Dis 185Suppl1 S96 S101.
17. M.M. Heimesaat S. Bereswill A. Fischer D. Fuchs D. Struck et al.2006 Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii J Immunol 177 8785 8795.
18. I.A. Khan J.D. Schwartzman T. Matsuura L.H. Kasper 1997 A dichotomous role for nitric oxide during acute Toxoplasma gondii infection in mice Proc Natl Acad Sci U S A 94 13955 13960.
19. F.J. Mennechet L.H. Kasper N. Rachinel W. Li A. Vandewalle et al.2002 Lamina propria CD4+ T lymphocytes synergize with murine intestinal epithelial cells to enhance proinflammatory response against an intracellular pathogen J Immunol 168 2988 2996.
20. O. Liesenfeld H. Kang D. Park T.A. Nguyen C.V. Parkhe et al.1999 TNF-alpha, nitric oxide and IFN-gamma are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii Parasite Immunol 21 365 376.
21. A. Vossenkamper D. Struck C. Alvarado-Esquivel T. Went K. Takeda et al.2004 Both IL-12 and IL-18 contribute to small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii, but IL-12 is dominant over IL-18 in parasite control Eur J Immunol 34 3197 3207.
22. M. Munoz M.M. Heimesaat K. Danker D. Struck U. Lohmann et al.2009 Interleukin (IL)-23 mediates Toxoplasma gondiiinduced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. 2 and IL-22 but independent of IL-17 J Exp Med 206 3047 3059.
23. D. Struck I. Frank S. Enders U. Steinhoff C. Schmidt A. Stallmach O. Liesenfeld M.M. Heimesaat 2012 Treatment with Interleukin-18 binding protein ameliorates Toxoplasma gondii-induced small intestinal pathology that is induced by bone marrow cell-derived Interleukin-18 Eur J Microbiol Immunol 2 249 257.
24. M.M. Heimesaat A. Fischer H.K. Jahn J. Niebergall M. Freudenberg et al.2007 Exacerbation of murine ileitis by Toll-like receptor 4 mediated sensing of lipopolysaccharide from commensal Escherichia coli Gut 56 941 948.
25. C. Erridge S.H. Duncan S. Bereswill M.M. Heimesaat 2010 The induction of colitis and ileitis in mice is associated with marked increases in intestinal concentrations of stimulants of TLRs 2, 4, and 5 PLoS One 5 e9125.
26. Haag LM , Fischer A, Otto B, Plickert R, Kühl AA et al.: Intestinal microbiota shifts towards elevated commensal Escherichia coli loads abrogate colonization resistance against Campylobacter jejuni in mice. PLoS One 7, e35988 (2012).
27. M.M. Heimesaat A. Fischer B. Siegmund A. Kupz J. Niebergall et al.2007 Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4 PLoS One 2 e662.
28. M.M. Heimesaat A. Nogai S. Bereswill R. Plickert A. Fischer et al.2010 MyD88/TLR9 mediated immunopathology and gut microbiota dynamics in a novel murine model of intestinal graft-versus-host disease Gut 59 1079 1087.
29. S. Bereswill M. Munoz A. Fischer R. Plickert L.M. Haag et al.2010 Anti-inflammatory effects of resveratrol, curcumin and simvastatin in acute small intestinal inflammation PLoS One 5 e15099.
30. L.M. Haag A. Fischer B. Otto U. Grundmann A.A. Kühl et al.2012 Campylobacter jejuni infection of infant mice: acute enterocolitis is followed by asymptomatic intestinal and extra-intestinal immune response Eur J Microbiol Immunol 2 2 11.
31. Bereswill S , Fischer A, Plickert R, Haag LM, Otto B et al.: Novel murine infection models provide deep insights into the “menage a trois” of Campylobacter jejuni, microbiota and host innate immunity. PLoS One 6, e20953 (2011).
32. P.I. Zigra V.E. Maipa Y.P. Alamanos 2007 Probiotics and remission of ulcerative colitis: a systematic review Neth J Med 65 411 418.
33. A.C. Senok A.Y. Ismaeel G.A. Botta 2005 Probiotics: facts and myths Clin Microbiol Infect 11 958 966.
34. S. Lebeer J. Vanderleyden S.C. De Keersmaecker 2010 Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens Nat Rev Microbiol 8 171 184.
35. I. Trebichavsky I. Splichal V. Rada A. Splichalova 2010 Modulation of natural immunity in the gut by Escherichia coli strain Nissle 1917 Nutr Rev 68 459 464.
36. A. Bleich J.P. Sundberg A. Smoczek R. von Wasielewski M.F. de Buhr et al.2008 Sensitivity to Escherichia coli Nissle 1917 in mice is dependent on environment and genetic background Int J Exp Pathol 89 45 54.
37. S.N. Ukena A.M. Westendorf W. Hansen M. Rohde R. Geffers et al.2005 The host response to the probiotic Escherichia coli strain Nissle 1917: specific up-regulation of the proinflammatory chemokine MCP-1 BMC Med Genet 6 43.
38. R.A. Welch V. Burland G. Plunkett 3rd P. Redford P. Roesch et al.2002 Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli Proc Natl Acad Sci U S A 99 17020 17024.
39. L. Grozdanov C. Raasch J. Schulze U. Sonnenborn G. Gottschalk et al.2004 Analysis of the genome structure of the non-pathogenic probiotic Escherichia coli strain Nissle 1917 J Bacteriol 186 5432 5441.
40. J. Sun F. Gunzer A.M. Westendorf J. Buer M. Scharfe et al.2005 Genomic peculiarity of coding sequences and metabolic potential of probiotic Escherichia coli strain Nissle 1917 inferred from raw genome data J Biotechnol 117 147 161.
41. E. Adam L. Delbrassine C. Bouillot V. Reynders A.C. Mailleux et al.2010 Probiotic Escherichia coli Nissle 1917 activates DC and prevents house dust mite allergy through a TLR4-dependent pathway Eur J Immunol 40 1995 2005.
42. H.S. Warren C. Fitting E. Hoff M. Adib-Conquy L. Beasley-Topliffe et al.2010 Resilience to bacterial infection: difference between species could be due to proteins in serum J Infect Dis 201 223 232.
43. K. Guenther E. Straube W. Pfister A. Guenther A. Huebler 2010 Severe sepsis after probiotic treatment with Escherichia coli NISSLE 1917 Pediatr Infect Dis J 29 188 189.