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Evolution und Infektionsbiologie der mit dem hämolytisch-urämischen Syndrom (HUS) assoziierten E.  coli (HUSEC)

Evolution and infection biology of hemolytic-uremic syndrome (HUS) associated E. coli (HUSEC)

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Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz Aims and scope

Zusammenfassung

Shigatoxin-produzierende Escherichia coli (STEC), die das hämolytisch-urämische Syndrom (HUS) hervorrufen, werden als HUSEC bezeichnet. Ihre außerordentliche Genomvariabilität, die treibende Kraft evolutionärer Veränderungen, ermöglicht ihnen eine schnelle Anpassung an sich ändernde Umweltbedingungen. Die am Institut für Hygiene in Münster etablierte HUSEC-Kollektion (http://www.ehec.org) umfasst 42 EHEC-Referenztypstämme (HUSEC001–HUSEC042). Die HUSEC-Kollektion stellt eine einzigartige Sammlung von Krankheitserregern dar und ist äußerst hilfreich für die Analyse evolutiver Diversifizierungen und konservierter Eigenschaften von STEC, die schwerste Wirtsschädigungen verursachen. Derartige genomische Eigenschaften schließen sich langsam entwickelnde Genloci und mobile Genelemente ein, die häufig für Virulenzfaktoren kodieren und durch horizontalen Gentransfer („Evolutionsbeschleuniger“) entstanden sind. Aktuelle Evolutionsmodelle weisen darauf hin, dass sich zahlreiche Ausbruchsstämme erst kürzlich entwickelt haben und dass hochpathogene HUSEC von weniger virulenten Vorläufern abstammen. Weitere Daten legen nahe, dass HUSEC kleine, effektive Populationsgrößen ausmachen. Die HUSEC-Kollektion ist darüber hinaus eine wertvolle Ressource, um Nicht-Shigatoxin-Virulenzfaktoren zu untersuchen.

Abstract

Shiga toxin (Stx)-producing Escherichia coli (STEC), which cause hemolytic-uremic syndrome (HUS), are designated as HUSEC. Their exceptional genome variability driven by evolutionary diversification permits fast adaptation to changed environmental conditions. The HUSEC collection (http://www.ehec.org), which has been established at the Institute for Hygiene in Münster, contains 42 EHEC reference strains (HUSEC001–HUSEC042). It represents a unique repository collection of pathogens and is extremely helpful for the analysis of evolutionary changes and fixed properties in the STEC that cause the most severe host injury. Such genomic attributes include slowly evolving loci, mobile genetic elements that often encode virulence factors and are assimilated via horizontal gene transfer. Current evolutionary models indicate that numerous outbreak strains evolved recently and that highly pathogenic HUSEC descend from less pathogenic progenitors. However, additional data suggest that HUSEC have small effective population sizes. The HUSEC collection is also a valuable resource with which to study important non-Shiga toxin virulence factors.

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Literatur

  1. Friedrich AW, Bielaszewska M, Zhang WL et al (2002) Escherichia coli harboring Shiga toxin 2 gene variants: frequency and association with clinical symptoms. J Infect Dis 185:74–84

    Article  PubMed  CAS  Google Scholar 

  2. Bielaszewska M, Friedrich AW, Aldick T et al (2006) Shiga toxin activatable by intestinal mucus in Escherichia coli isolated from humans: predictor for a severe clinical outcome. Clin Infect Dis 43:1160–1167

    Article  PubMed  CAS  Google Scholar 

  3. Mellmann A, Bielaszewska M, Köck R et al (2008) Analysis of collection of hemolytic uremic syndrome-associated enterohemorrhagic Escherichia coli. Emerg Infect Dis 14:1287–1290

    Article  PubMed  Google Scholar 

  4. Ammon A, Petersen LR, Karch H (1999) A large outbreak of hemolytic uremic syndrome caused by an unusual sorbitol-fermenting strain of Escherichia coli O157:H. J Infect Dis 179:1274–1277

    Article  PubMed  CAS  Google Scholar 

  5. Bielaszewska M, Mellmann A, Zhang W et al (2011) Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. Lancet Infect Dis 11:671–676

    PubMed  CAS  Google Scholar 

  6. Wirth T, Falush D, Lan R et al (2006) Sex and virulence in Escherichia coli: an evolutionary perspective. Mol Microbiol 60:1136–1151

    Article  PubMed  CAS  Google Scholar 

  7. Brunder W, Karch H (2000) Genome plasticity in Enterobacteriaceae. Int J Med Microbiol 290:153–165

    Article  PubMed  CAS  Google Scholar 

  8. Dobrindt U (2005) (Patho-)Genomics of Escherichia coli. Int J Med Microbiol 295:357–371

    Article  PubMed  CAS  Google Scholar 

  9. Dobrindt U, Agerer F, Michaelis K et al (2003) Analysis of genome plasticity in pathogenic and commensal Escherichia coli isolates by use of DNA arrays. J Bacteriol 185:1831–1840

    Article  PubMed  CAS  Google Scholar 

  10. Mellmann A, Bielaszewska M, Karch H (2008) Intrahost genome alterations in enterohemorrhagic Escherichia coli. Gastroenterology 136:1925–1938

    Article  Google Scholar 

  11. Ahmed N, Dobrindt U, Hacker J, Hasnain SE (2008) Genomic fluidity and pathogenic bacteria: applications in diagnostics, epidemiology and intervention. Nat Rev Microbiol 6:387–394

    Article  PubMed  CAS  Google Scholar 

  12. Dobrindt U, Hochhut B, Hentschel U, Hacker J (2004) Genomic islands in pathogenic and environmental microorganisms. Nat Rev Microbiol 2:414–424

    Article  PubMed  CAS  Google Scholar 

  13. Hacker J, Hentschel U, Dobrindt U (2003) Prokaryotic chromosomes and disease. Science 301:790–793

    Article  PubMed  CAS  Google Scholar 

  14. Mellmann A, Lu S, Karch H et al (2008) Recycling of Shiga toxin 2 genes in sorbitol-fermenting enterohemorrhagic Escherichia coli O157:NM. Appl Environ Microbiol 74:67–72

    Article  PubMed  CAS  Google Scholar 

  15. Bielaszewska M, Middendorf B, Tarr PI et al (2011) Chromosomal instability in enterohaemorrhagic Escherichia coli O157:H7: impact on adherence, tellurite resistance and colony phenotype. Mol Microbiol 79:1024–1044

    Article  PubMed  CAS  Google Scholar 

  16. Janka A, Becker G, Sonntag AK et al (2005) Presence and characterization of a mosaic genomic island which distinguishes sorbitol-fermenting enterohemorrhagic Escherichia coli O157:H from E. coli O157:H7. Appl Environ Microbiol 71:4875–4878

    Article  PubMed  CAS  Google Scholar 

  17. Mellmann A, Harmsen D, Cummings CA et al (2011) Prospective genomic characterization of the German enterohemorrhagic Escherichia coli O104:H4 outbreak by rapid next generation sequencing technology. PLoS One 6:e22751

    Article  PubMed  CAS  Google Scholar 

  18. Reid SD, Herbelin CJ, Bumbaugh AC et al (2000) Parallel evolution of virulence in pathogenic Escherichia coli. Nature 406:64–67

    Article  PubMed  CAS  Google Scholar 

  19. Schubert S, Darlu P, Clermont O et al (2009) Role of intraspecies recombination in the spread of pathogenicity islands within the Escherichia coli species. PLoS Pathog 5:e1000257

    Article  PubMed  Google Scholar 

  20. Mira A, Pushker R, Rodriguez-Valera F (2006) The neolithic revolution of bacterial genomes. Trends Microbiol 14:200–206

    Article  PubMed  CAS  Google Scholar 

  21. Brunder W, Schmidt H, Frosch M, Karch H (1999) The large plasmids of Shiga-toxin-producing Escherichia coli (STEC) are highly variable genetic elements. Microbiology 145:1005–1014

    Article  PubMed  CAS  Google Scholar 

  22. Brunder W, Khan AS, Hacker J, Karch H (2001) Novel type of fimbriae encoded by the large plasmid of sorbitol-fermenting enterohemorrhagic Escherichia coli O157:H. Infect Immun 69:4447–4457

    Article  PubMed  CAS  Google Scholar 

  23. Brunder W, Schmidt H, Karch H (1997) EspP, a novel extracellular serine protease of enterohaemorrhagic Escherichia coli O157:H7 cleaves human coagulation factor V. Mol Microbiol 24:767–778

    Article  PubMed  CAS  Google Scholar 

  24. Schmidt H, Beutin L, Karch H (1995) Molecular analysis of the plasmid-encoded hemolysin of Escherichia coli O157:H7 strain EDL 933. Infect Immun 63:1055–1061

    PubMed  CAS  Google Scholar 

  25. Karch H, Schmidt H, Janetzki-Mittmann C et al (1999) Shiga toxins even when different are encoded at identical positions in the genomes of related temperate bacteriophages. Mol Gen Genet 262:600–607

    Article  PubMed  CAS  Google Scholar 

  26. Schmidt H, Hensel M (2004) Pathogenicity islands in bacterial pathogenesis. Clin Microbiol Rev 17:14–56

    Article  PubMed  CAS  Google Scholar 

  27. Brzuszkiewicz E, Gottschalk G, Ron E et al (2009) Adaptation of pathogenic E. coli to various niches: genome flexibility is the key. Genome Dyn 6:110–125

    Article  PubMed  CAS  Google Scholar 

  28. Groisman EA, Ochman H (1996) Pathogenicity islands: bacterial evolution in quantum leaps. Cell 87:791–794

    Article  PubMed  CAS  Google Scholar 

  29. Tenaillon O, Skurnik D, Picard B, Denamur E (2010) The population genetics of commensal Escherichia coli. Nat Rev Microbiol 8:207–217

    Article  PubMed  CAS  Google Scholar 

  30. Karch H, Böhm H, Schmidt H et al (1993) Clonal structure and pathogenicity of Shiga-like toxin-producing, sorbitol-fermenting Escherichia coli O157:H. J Clin Microbiol 31:1200–1205

    PubMed  CAS  Google Scholar 

  31. Schmidt H, Geitz C, Tarr PI et al (1999) Non-O157:H7 pathogenic Shiga toxin-producing Escherichia coli: phenotypic and genetic profiling of virulence traits and evidence for clonality. J Infect Dis 179:115–123

    Article  PubMed  CAS  Google Scholar 

  32. Zhang WL, Bielaszewska M, Bockemühl J et al (2000) Molecular analysis of H antigens reveals that human diarrheagenic Escherichia coli O26 strains that carry the eae gene belong to the H11 clonal complex. J Clin Microbiol 38:2989–2993

    PubMed  CAS  Google Scholar 

  33. Jenke C, Harmsen D, Weniger T et al (2010) Phylogenetic analysis of enterohemorrhagic Escherichia coli O157, Germany, 1987–2008. Emerg Infect Dis 16:610–616

    Article  PubMed  CAS  Google Scholar 

  34. Jenke C, Leopold SR, Weniger T et al (2012) Identification of intermediate in evolutionary model of enterohemorrhagic Escherichia coli O157. Emerg Infect Dis 18:582–588

    Article  PubMed  Google Scholar 

  35. Leopold SR, Magrini V, Holt NJ et al (2009) A precise reconstruction of the emergence and constrained radiations of Escherichia coli O157 portrayed by backbone concatenomic analysis. Proc Natl Acad Sci U S A 106:8713–8718

    Article  PubMed  CAS  Google Scholar 

  36. Bielaszewska M, Sinha B, Kuczius T, Karch H (2005) Cytolethal distending toxin from Shiga toxin-producing Escherichia coli O157 causes irreversible G2/M arrest, inhibition of proliferation, and death of human endothelial cells. Infect Immun 73:552–562

    Article  PubMed  CAS  Google Scholar 

  37. Janka A, Bielaszewska M, Dobrindt U et al (2003) Cytolethal distending toxin gene cluster in enterohemorrhagic Escherichia coli O157:H and O157:H7: characterization and evolutionary considerations. Infect Immun 71:3634–3638

    Article  PubMed  CAS  Google Scholar 

  38. Paton AW, Beddoe T, Thorpe CM et al (2006) AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP. Nature 443:548–552

    Article  PubMed  CAS  Google Scholar 

  39. Merkel V, Ohder B, Bielaszewska M et al (2010) Distribution and phylogeny of immunoglobulin-binding protein G in Shiga toxin-producing Escherichia coli and its association with adherence phenotypes. Infect Immun 78:3625–3636

    Article  PubMed  CAS  Google Scholar 

  40. Brockmeyer J, Aldick T, Soltwisch J et al (2011) Enterohaemorrhagic Escherichia coli haemolysin is cleaved and inactivated by serine protease Espα. Environ Microbiol 13:1327–1341

    Article  PubMed  CAS  Google Scholar 

  41. Ruiz-Perez F, Wahid R, Faherty CS et al (2011) Serine protease autotransporters from Shigella flexneri and pathogenic Escherichia coli target a broad range of leukocyte glycoproteins. Proc Natl Acad Sci U S A 108:12881–12886

    Article  PubMed  CAS  Google Scholar 

  42. Bauwens A, Betz J, Meisen I et al (2012) Facing glycosphingolipid-Shiga toxin interaction: dire straits for endothelial cells of the human vasculature. Cell Mol Life Sci, doi:10.1007/s00018-012-1060-z

  43. Müthing J, Schweppe CH, Karch H, Friedrich AW (2009) Shiga toxins, glycosphingolipid diversity, and endothelial cell injury. Thromb Haemost 101:252–264

    PubMed  Google Scholar 

  44. Müthing J, Meisen I, Zhang W et al (2012) Promiscuous Shiga toxin 2e and its intimate relationship to Forssman. Glycobiology 22:849–862

    Article  PubMed  Google Scholar 

  45. Lopez EL, Contrini MM, Glatstein E et al (2012) An epidemiologic surveillance of Shiga-like toxin-producing Escherichia coli infection in Argentinean children: risk factors and serum Shiga-like toxin 2 values. Pediatr Infect Dis J 31:20–24

    Article  PubMed  Google Scholar 

  46. Brigotti M, Carnicelli D, Ravanelli E et al (2008) Interactions between Shiga toxins and human polymorphonuclear leukocytes. J Leukoc Biol 84:1019–1027

    Article  PubMed  CAS  Google Scholar 

  47. Schweppe CH, Hoffmann P, Nofer JR et al (2010) Neutral glycosphingolipids in human blood: a precise mass spectrometry analysis with special reference to lipoprotein-associated Shiga toxin receptors. J Lipid Res 51:2282–2294

    Article  PubMed  CAS  Google Scholar 

  48. Bauwens A, Bielaszewska M, Kemper B et al (2011) Differential cytotoxic actions of Shiga toxin 1 and Shiga toxin 2 on microvascular and macrovascular endothelial cells. Thromb Haemost 105:515–528

    Article  PubMed  CAS  Google Scholar 

  49. Betz J, Bauwens A, Kunsmann L et al (2012) Uncommon membrane distribution of Shiga toxin glycosphingolipid receptors in toxin-sensitive human glomerular microvascular endothelial cells. Biol Chem 393:133–147

    Article  PubMed  CAS  Google Scholar 

  50. Betz J, Bielaszewska M, Thies A et al (2011) Shiga toxin glycosphingolipid receptors in microvascular and macrovascular endothelial cells: differential association with membrane lipid raft microdomains. J Lipid Res 52:618–634

    Article  PubMed  CAS  Google Scholar 

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Danksagungen

Die infektionsepidemiologischen Arbeiten wurden von den BMBF-Netzwerken FBI-Zoo (FKZ: 01KI1012B) und der Nationalen Forschungsplattform für Zoonosen (FKZ: 01KI1106) sowie von der Medizinischen Fakultät der Universität Münster (9817044) gefördert. Herrn Professor Dr. med. Georg Peters, Universität Münster, danken wir für die kritische Durchsicht des Manuskriptes, die hilfreichen Diskussionen und für die kontinuierliche Unterstützung unserer Forschungsprojekte. Den Kolleginnen und Kollegen vom RKI in Berlin und der Außenstelle Wernigerode möchten wir für die hervorragende langjährige Zusammenarbeit danken. Weiterhin gilt unser Dank Frau Ina Fichtner, Institut für Hygiene, Universitätsklinikum Münster, für die Hilfe bei der Erstellung des Manuskriptes.

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Karch, H., Müthing, J., Dobrindt, U. et al. Evolution und Infektionsbiologie der mit dem hämolytisch-urämischen Syndrom (HUS) assoziierten E.  coli (HUSEC). Bundesgesundheitsbl. 56, 8–14 (2013). https://doi.org/10.1007/s00103-012-1586-0

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