Molecular Genetics and Genomics

, Volume 283, Issue 5, pp 469–484 | Cite as

A virulent parent with probiotic progeny: comparative genomics of Escherichia coli strains CFT073, Nissle 1917 and ABU 83972

  • Rebecca Munk Vejborg
  • Carsten Friis
  • Viktoria Hancock
  • Mark A. Schembri
  • Per KlemmEmail author
Original Paper


Escherichia coli is a highly versatile species encompassing a diverse spectrum of strains, i.e. from highly virulent isolates causing serious infectious diseases to commensals and probiotic strains. Although much is known about bacterial pathogenicity in E. coli, the understanding of which genetic determinants differentiates a virulent from an avirulent strain still remains limited. In this study we designed a new comparative genomic hybridization microarray based on 31 sequenced E. coli strains and used it to compare two E. coli strains used as prophylactic agents (i.e. Nissle 1917 and 83972) with the highly virulent uropathogen CFT073. Only relatively minor genetic variations were found between the isolates, suggesting that the three strains may have originated from the same virulent ancestral parent. Interestingly, Nissle 1917 (a gut commensal strain) was more similar to CFT073 with respect to genotype and phenotype than 83972 (an asymptomatic bacteriuria strain). The study indicates that genetic variations (e.g. mutations) and expression differences, rather than genomic content per se, contribute to the divergence in disease-causing ability between these strains. This has implications for the use of virulence factors in epidemiological research, and emphasizes the need for more comparative genomic studies of closely related strains to compare their virulence potential.


CFT073 Nissle 1917 ABU 83972 Comparative genomic hybridization analysis Escherichia coli Urinary tract infection 



This work was supported by grants from Lundbeckfonden (grant no. R17-A1603) and the Danish Medical Research Council (271-06-0555). We also wish to thank the Danish Center for Scientific Computing (DCSC) and the Danish Natural Science Research Council (FNU grant 26-06-0349). MAS is supported by a grant from the National Health and Medical Research Council of Australia (569676).

Supplementary material

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  1. Alteri CJ, Mobley HL (2007) Quantitative profile of the uropathogenic Escherichia coli outer membrane proteome during growth in human urine. Infect Immun 75(6):2679–2688PubMedGoogle Scholar
  2. Andersson P, Engberg I, Lidin-Janson G, Lincoln K, Hull R, Hull S, Svanborg C (1991) Persistence of Escherichia coli bacteriuria is not determined by bacterial adherence. Infect Immun 59:2915–2921PubMedGoogle Scholar
  3. Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL (2008) GenBank. Nucleic Acids Res 36:D25–D30CrossRefPubMedGoogle Scholar
  4. Bhargava S, Johnson BB, Hwang J, Harris TA, George AS, Muir A, Dorff J, Okeke IN (2009) Heat-resistant agglutinin 1 is an accessory enteroaggregative Escherichia coli colonization factor. J Bacteriol 191:4934–4942CrossRefPubMedGoogle Scholar
  5. Chen SL, Hung CS, Xu J, Reigstad CS, Magrini V, Sabo A, Blasiar D, Bieri T, Meyer RR, Ozersky P, Armstrong JR, Fulton RS, Latreille JP, Spieth J, Hooton TM, Mardis ER, Hultgren SJ, Gordon JI (2006) Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli a comparative genomics approach. Proc Natl Acad Sci USA 103:5977–5982CrossRefPubMedGoogle Scholar
  6. Chouikha I, Germon P, Bree A, Gilot P, Moulin-Schouleur M, Schouler C (2006) A selC-associated genomic island of the extraintestinal avian pathogenic Escherichia coli strain BEN2908 is involved in carbohydrate uptake and virulence. J Bacteriol 188:977–987CrossRefPubMedGoogle Scholar
  7. Cirl C, Wieser A, Yadav M, Duerr S, Schubert S, Fischer H, Stappert D, Wantia N, Rodriguez N, Wagner H, Svanborg C, Miethke T (2008) Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins. Nat Med 14:399–406CrossRefPubMedGoogle Scholar
  8. Connell H, Agace W, Klemm P, Schembri M, Marild S, Svanborg C (1996) Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract. Proc Natl Acad Sci USA 93:9827–9832CrossRefPubMedGoogle Scholar
  9. Croxen MA, Finlay BB (2010) Molecular mechanisms of Escherichia coli pathogenicity. Nat Rev Microbiol 8:26–38CrossRefPubMedGoogle Scholar
  10. Danese PN, Pratt LA, Dove SL, Kolter R (2000) The outer membrane protein, antigen 43, mediates cell-to-cell interactions within Escherichia coli biofilms. Mol Microbiol 37:424–432CrossRefPubMedGoogle Scholar
  11. Dobrindt U, Hentschel U, Kaper JB, Hacker J (2002) Genome plasticity in pathogenic and nonpathogenic enterobacteria. Curr Top Microbiol Immunol 264:157–175PubMedGoogle Scholar
  12. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5:R80CrossRefPubMedGoogle Scholar
  13. Gottesman S, Stout V (1991) Regulation of capsular polysaccharide synthesis in Escherichia coli K12. Mol Microbiol 5:1599–1606CrossRefPubMedGoogle Scholar
  14. Grozdanov L, Zahringer U, Blum-Oehler G, Brade L, Henne A, Knirel YA, Schombel U, Schulze J, Sonnenborn U, Gottschalk G, Hacker J, Rietschel ET, Dobrindt U (2002) A single nucleotide exchange in the wzy gene is responsible for the semirough O6 lipopolysaccharide phenotype and serum sensitivity of Escherichia coli strain Nissle 1917. J Bacteriol 184:5912–5925CrossRefPubMedGoogle Scholar
  15. Grozdanov L, Raasch C, Schulze J, Sonnenborn U, Gottschalk G, Hacker J, Dobrindt U (2004) Analysis of the genome structure of the nonpathogenic probiotic Escherichia coli strain Nissle 1917. J Bacteriol 186:5432–5441CrossRefPubMedGoogle Scholar
  16. Hacker J, Carniel E (2001) Ecological fitness, genomic islands and bacterial pathogenicity. A Darwinian view of the evolution of microbes. EMBO Rep 2:376–381PubMedGoogle Scholar
  17. Hafez M, Hayes K, Goldrick M, Warhurst G, Grencis R, Roberts IS (2009) The K5 capsule of Escherichia coli strain Nissle 1917 is important in mediating interactions with intestinal epithelial cells and chemokine induction. Infect Immun 77:2995–3003CrossRefPubMedGoogle Scholar
  18. Hagan EC, Mobley HL (2007) Uropathogenic Escherichia coli outer membrane antigens expressed during urinary tract infection. Infect Immun 75:3941–3949CrossRefPubMedGoogle Scholar
  19. Hancock V, Klemm P (2007) Global gene expression profiling of asymptomatic bacteriuria Escherichia coli during biofilm growth in human urine. Infect Immun 75:966–976CrossRefPubMedGoogle Scholar
  20. Hancock V, Ferrières L, Klemm P (2007) Biofilm formation by asymptomatic and virulent urinary tract infectious Escherichia coli strains. FEMS Microbiol Lett 267:30–37CrossRefPubMedGoogle Scholar
  21. Hancock V, Seshasayee AS, Ussery DW, Luscombe NM, Klemm P (2008) Transcriptomics and adaptive genomics of the asymptomatic bacteriuria Escherichia coli strain 83972. Mol Genet Genomics 279:523–534CrossRefPubMedGoogle Scholar
  22. Hancock V, Nielsen EM, Krag L, Engberg J, Klemm P (2009) Comparative analysis of antibiotic resistance and phylogenetic group patterns in human and porcine urinary tract infectious Escherichia coli. APMIS 117:786–790CrossRefPubMedGoogle Scholar
  23. Hannan TJ, Mysorekar IU, Chen SL, Walker JN, Jones JM, Pinkner JS, Hultgren SJ, Seed PC (2008) LeuX tRNA-dependent and -independent mechanisms of Escherichia coli pathogenesis in acute cystitis. Mol Microbiol 67:116–128Google Scholar
  24. Hentschel U, Hacker J (2001) Pathogenicity islands: the tip of the iceberg. Microbes Infect 3:545–548CrossRefPubMedGoogle Scholar
  25. Hobohm U, Scharf M, Schneider R, Sander C (1992) Selection of representative protein data sets. Protein Sci 1:409–417PubMedCrossRefGoogle Scholar
  26. Hull RA, Rudy DC, Donovan WH, Wieser IE, Stewart C, Darouiche RO (1999) Virulence properties of Escherichia coli 83972, a prototype strain associated with asymptomatic bacteriuria. Infect Immun 67:429–432PubMedGoogle Scholar
  27. Hull R, Rudy D, Donovan W, Svanborg C, Wieser I, Stewart C, Darouiche R (2000) Urinary tract infection prophylaxis using Escherichia coli 83972 in spinal cord injured patients. J Urol 163:872–877CrossRefPubMedGoogle Scholar
  28. Johanson IM, Plos K, Marklund BI, Svanborg C (1993) Pap, papG and prsG DNA sequences in Escherichia coli from the fecal flora and the urinary tract. Microb Pathog 15:121–129CrossRefPubMedGoogle Scholar
  29. Kaper JB, Nataro JP, Mobley HL (2004) Pathogenic Escherichia coli. Nat Rev Microbiol 2:123–140CrossRefPubMedGoogle Scholar
  30. Klemm P, Roos V, Ulett GC, Svanborg C, Schembri MA (2006) Molecular characterization of the Escherichia coli asymptomatic bacteriuria strain 83972: the taming of a pathogen. Infect Immun 74:781–785CrossRefPubMedGoogle Scholar
  31. Klemm P, Hancock V, Schembri MA (2007) Mellowing out: adaptation to commensalism by Escherichia coli asymptomatic bacteriuria strain 83972. Infect Immun 75:3688–3695CrossRefPubMedGoogle Scholar
  32. Kruis W, Schutz E, Fric P, Fixa B, Judmaier G, Stolte M (1997) Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 11:853–858CrossRefPubMedGoogle Scholar
  33. Lane MC, Mobley HL (2007) Role of P-fimbrial-mediated adherence in pyelonephritis and persistence of uropathogenic Escherichia coli (UPEC) in the mammalian kidney. Kidney Int 72:19–25CrossRefPubMedGoogle Scholar
  34. Larsen TS, Krogh A (2003) EasyGene—a prokaryotic gene finder that ranks ORFs by statistical significance. BMC Bioinformatics 4:21CrossRefPubMedGoogle Scholar
  35. Lindberg U, Hanson LA, Jodal U, Lidin-Janson G, Lincoln K, Olling S (1975) Asymptomatic bacteriuria in schoolgirls. II. Differences in Escherichia coli causing asymptomatic bacteriuria. II. Differences in Escherichia coli causing asymptomatic bacteriuria. Acta Paediatr Scand 64:432–436CrossRefPubMedGoogle Scholar
  36. Lloyd AL, Rasko DA, Mobley HL (2007) Defining genomic islands and uropathogen-specific genes in uropathogenic Escherichia coli. J Bacteriol 189:3532–3546CrossRefPubMedGoogle Scholar
  37. Lloyd AL, Henderson TA, Vigil PD, Mobley HL (2009) Genomic islands of uropathogenic Escherichia coli contribute to virulence. J Bacteriol 191:3469–3481CrossRefPubMedGoogle Scholar
  38. Malchow HA (1997) Crohn’s disease and Escherichia coli. A new approach in therapy to maintain remission of colonic Crohn’s disease? J Clin Gastroenterol 25:653–658CrossRefPubMedGoogle Scholar
  39. Middendorf B, Hochhut B, Leipold K, Dobrindt U, Blum-Oehler G, Hacker J (2004) Instability of pathogenicity islands in uropathogenic Escherichia coli 536. J Bacteriol 186:3086–3096CrossRefPubMedGoogle Scholar
  40. Mobley HL, Green DM, Trifillis AL, Johnson DE, Chippendale GR, Lockatell CV, Jones BD, Warren JW (1990) Pyelonephritogenic Escherichia coli and killing of cultured human renal proximal tubular epithelial cells: role of hemolysin in some strains. Infect Immun 58:1281–1289PubMedGoogle Scholar
  41. Monteiro C, Saxena I, Wang X, Kader A, Bokranz W, Simm R, Nobles D, Chromek M, Brauner A, Brown RM Jr, Romling U (2009) Characterization of cellulose production in Escherichia coli Nissle 1917 and its biological consequences. Environ Microbiol 11:1105–1116CrossRefPubMedGoogle Scholar
  42. Nielsen P, Krogh A (2005) Large-scale prokaryotic gene prediction and comparison to genome annotation. Bioinformatics 21:4322–4329CrossRefPubMedGoogle Scholar
  43. Nissle A (1918) Die antagonistische Behandlungen chronischer Darmstörungen mir Kolibakterien. Med Klein 2:29–30Google Scholar
  44. Nissle A (1925) Weiteres über Grundlagen und Praxis der Mutaflorbehandlung. DMW 4:1809–1813Google Scholar
  45. Prigent-Combaret C, Prensier G, Le Thi TT, Vidal O, Lejeune P, Dorel C (2000) Developmental pathway for biofilm formation in curli-producing Escherichia coli strains: role of flagella, curli and colanic acid. Environ Microbiol 2:450–464CrossRefPubMedGoogle Scholar
  46. Roos V, Klemm P (2006) Global gene expression profiling of the asymptomatic bacteriuria Escherichia coli strain 83972 in the human urinary tract. Infect Immun 74:3565–3575CrossRefPubMedGoogle Scholar
  47. Roos V, Ulett GC, Schembri MA, Klemm P (2006) The asymptomatic bacteriuria Escherichia coli strain 83972 out-competes UPEC strains in human urine. Infect Immun 74:615–624CrossRefPubMedGoogle Scholar
  48. Russo TA, Carlino UB, Johnson JR (2001) Identification of a new iron-regulated virulence gene, ireA, in an extraintestinal pathogenic isolate of Escherichia coli. Infect Immun 69:6209–6216CrossRefPubMedGoogle Scholar
  49. Schultz M (2008) Clinical use of E. coli Nissle 1917 in inflammatory bowel disease. Inflamm Bowel Dis 14:1012–1018CrossRefPubMedGoogle Scholar
  50. Snyder JA, Haugen BJ, Buckles EL, Lockatell CV, Johnson DE, Donnenberg MS, Welch RA, Mobley HL (2004) Transcriptome of uropathogenic Escherichia coli during urinary tract infection. Infect Immun 72:6373–6381CrossRefPubMedGoogle Scholar
  51. Sonnenborn U, Schulze J (2009) The non-pathogenic Escherichia coli strain Nissle 1917—features of a versatile probiotic. Microb Ecol Health Dis 21:122–158CrossRefGoogle Scholar
  52. Stamm WE (1991) Catheter-associated urinary tract infections: epidemiology, pathogenesis, and prevention. Am J Med 91:65S–71SCrossRefPubMedGoogle Scholar
  53. Stapleton A, Moseley S, Stamm WE (1991) Urovirulence determinants in Escherichia coli isolates causing first-episode and recurrent cystitis in women. J Infect Dis 163:773–779PubMedGoogle Scholar
  54. Stout V, Torres-Cabassa A, Maurizi MR, Gutnick D, Gottesman S (1991) RcsA, an unstable positive regulator of capsular polysaccharide synthesis. J Bacteriol 173:1738–1747PubMedGoogle Scholar
  55. Sun J, Gunzer F, Westendorf AM, Buer J, Scharfe M, Jarek M, Gossling F, Blocker H, Zeng AP (2005) Genomic peculiarity of coding sequences and metabolic potential of probiotic Escherichia coli strain Nissle 1917 inferred from raw genome data. J Biotechnol 117:147–161CrossRefPubMedGoogle Scholar
  56. Sunden F, Hakansson L, Ljunggren E, Wullt B (2006) Bacterial interference—is deliberate colonization with Escherichia coli 83972 an alternative treatment for patients with recurrent urinary tract infection? Int J Antimicrob Agents 28(Suppl 1):S26–S29CrossRefPubMedGoogle Scholar
  57. Tischler AD, Camilli A (2004) Cyclic diguanylate (c-di-GMP) regulates Vibrio cholerae biofilm formation. Mol Microbiol 53:857–869CrossRefPubMedGoogle Scholar
  58. Tischler AD, Camilli A (2005) Cyclic diguanylate regulates Vibrio cholerae virulence gene expression. Infect Immun 73:5873–5882CrossRefPubMedGoogle Scholar
  59. Tseng CC, Huang JJ, Wang MC, Wu AB, Ko WC, Chen WC, Wu JJ (2007) PapG II adhesin in the establishment and persistence of Escherichia coli infection in mouse kidneys. Kidney Int 71:764–770CrossRefPubMedGoogle Scholar
  60. Vejborg RM, Bernbom N, Gram L, Klemm P (2008) Anti-adhesive properties of fish tropomyosins. J Appl Microbiol 105:141–150CrossRefPubMedGoogle Scholar
  61. Vianney A, Jubelin G, Renault S, Dorel C, Lejeune P, Lazzaroni JC (2005) Escherichia coli tol and rcs genes participate in the complex network affecting curli synthesis. Microbiology 151:2487–2497CrossRefPubMedGoogle Scholar
  62. von Bargen K, Polidori M, Becken U, Huth G, Prescott JF, Haas A (2009) Rhodococcus equi virulence-associated protein A is required for diversion of phagosome biogenesis but not for cytotoxicity. Infect Immun 77:5676–5681CrossRefGoogle Scholar
  63. Welch RA, Burland V, Plunkett G 3rd, Redford P, Roesch P, Rasko D, Buckles EL, Liou SR, Boutin A, Hackett J, Stroud D, Mayhew GF, Rose DJ, Zhou S, Schwartz DC, Perna NT, Mobley HL, Donnenberg MS, Blattner FR (2002) Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci USA 99:17020–17024CrossRefPubMedGoogle Scholar
  64. Wernersson R, Nielsen HB (2005) OligoWiz 2.0—integrating sequence feature annotation into the design of microarray probes. Nucleic Acids Res 33:W611–W615CrossRefPubMedGoogle Scholar
  65. Wernersson R, Juncker AS, Nielsen HB (2007) Probe selection for DNA microarrays using OligoWiz. Nat Protoc 2:2677–2691CrossRefPubMedGoogle Scholar
  66. Zdziarski J, Svanborg C, Wullt B, Hacker J, Dobrindt U (2008) Molecular basis of commensalism in the urinary tract: low virulence or virulence attenuation? Infect Immun 76:695–703CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Rebecca Munk Vejborg
    • 1
  • Carsten Friis
    • 1
  • Viktoria Hancock
    • 1
  • Mark A. Schembri
    • 2
  • Per Klemm
    • 1
    Email author
  1. 1.DTU FoodTechnical University of DenmarkLyngbyDenmark
  2. 2.School of Chemistry and Molecular BiosciencesUniversity of QueenslandBrisbaneAustralia

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