Pediatric Nephrology

, Volume 6, Issue 6, pp 587–596 | Cite as

The molecular study of bacterial virulence: a review of current approaches, illustrated by the study of adhesion in uropathogenicEscherichia coli

  • R. John Roche
  • E. Richard Moxon
Basic Science Review

abstract

Pathogenic bacteria coexist with their hosts in a relationship which most frequently allows persistence of the bacteria without causing disease. In a small proportion of colonised individuals the complex mutual interaction between microbe and host is upset, leading to disease in the host. The investigation of bacterial virulence determinants and their genetic control at the molecular level is an important facet of the development of strategies to combat disease. This review focuses on the investigation of a single pathogenic organism as a means of illustrating modern approaches to the investigation of bacterial virulence. The importance of uropathogenicEscherichia coli in causing acute and recurrent pyelonephritis with the consequent morbidity of chronic renal failure is well established. Pyelonephritis-associated (Pap) pili are likely to be critical virulence factors in uropathogenicE. coli. The evidence for their role in pathogenicity and the control of their expression at the molecular genetic level is discussed.

Key words

UropathogenicEscherichia coli Pyelonephritis Adhesion Pyelonephritis-associated (Pap) pili Virulence Molecular genetics 

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References

  1. 1.
    Stamey TA, Sexton CC (1975) The role of vaginal colonization with enterobacteriaceae in recurrent urinary infections. J Urol 113: 214–217Google Scholar
  2. 2.
    Fowler JE Jr, Stamey TA (1977) Studies of introital colonization in women with recurrent urinary infections. VII. The role of bacterial adherence. J Urol 117: 472–476Google Scholar
  3. 3.
    Bjorksten B, Kaijser B (1978) Interaction of human serum and neutrophils withEscherichia coli strains: differences between strains isolated from urine of patients with pyelonephritis or asymptomatic bacteriuria. Infect Immun 22: 308–311Google Scholar
  4. 4.
    Hughes C, Hacker J, Roberts A, Geobel W (1983) Hemolysin production as a virulence marker in symptomatic and asymptomatic urinary tract infections caused byEscherichia coli. Infect Immun 21: 546–551Google Scholar
  5. 5.
    Davies DL, Falkiner FR, Hardy KG (1981) Colicin V production by clinical isolates ofEscherichia coli. Infect Immun 31: 574–579Google Scholar
  6. 6.
    Kaijser B, Hanson LA, Jodal U, Lidin-Janson G, Robbins JB (1977) Frequency ofE. coli K antigens in urinary tract infections in children. Lancet II: 663–664Google Scholar
  7. 7.
    Svanborg Eden C, Hanson LA, Jodal U, Lindberg U, Sohl Akerlund A (1977) Variable adherence to normal human urinary tract epithelial cells ofEscherichia coli strains associated with various forms of urinary tract infection. Lancet II: 490–492Google Scholar
  8. 8.
    Svanborg Eden C, Eriksson B, Hanson LA, Jodal U, Kaijser B, Lindin Janson G Lindberg U, Olling S (1978) Adhesion to normal uroepithelial cells ofEscherichia coli from children with various forms of urinary tract infection. J Pediatr 93: 398–403Google Scholar
  9. 9.
    Gordon DM, Riley MA (1992) A theoretical and experimental analysis of bacterial growth in the bladder. Mol Microbiol 6: 555–562Google Scholar
  10. 10.
    Svanborg Eden C, Hansson HA (1978)Escherichia coli pili as possible mediators of attachment to human urinary tract epithelial cells. Infect Immun 21: 229–237Google Scholar
  11. 11.
    Schoolnik GK (1990) The role of bacterial adherence in urinary tract infections. In: Neu HC (ed) New antibacterial strategies. Churchill Livingstone, New York, pp 111–120Google Scholar
  12. 12.
    Orskov I, Ferencz A, Orskov F (1980) Tamm-Horsfall protein or uromucoid is the normal urinary slime that traps type I fimbriatedEscherichia coli. Lancet I: 887Google Scholar
  13. 13.
    Bosch JF van der, Verboom-Sohmer U, Postma P, Graaff J de, MacLaren DM (1980) Mannose-sensitive and mannose-resistant adherence to human uroepithelial cells and urinary virulence ofEscherichia coli. Infect Immun 29: 226–233Google Scholar
  14. 14.
    Leffler H, Svanborg Eden C (1980) Chemical identification of a glycosphingolipid receptor forEscherichia coli attaching to human urinary tract epithelial cells and agglutinating human erythrocytes. FEMS Microbiol Lett 8: 127–134Google Scholar
  15. 15.
    Kallenius G, Mollby R, Svenson SB, Winberg J, Lundblad A, Svensson S, Cedergren B (1980) The Pk antigen as receptor for the haemagglutinin of pyelonephriticEscherichia coli. FEMS Microbiol Lett 7: 297–302Google Scholar
  16. 16.
    Labigne-Roussel A, Falkow S (1988) Distribution and degree of heterogeneity of the afimbrial-adhesin-encoding operon (afa) among uropathogenicEscherichia coli isolates. Infect Immun 56: 640–648Google Scholar
  17. 17.
    Nowicki B, Labigne A, Moseley S, Hull R, Hull S, Moulds J (1990) The Dr hemagglutinin, afimbrial adhesins AFA-I and AFA-III, and F1845 fimbriae of uropathogenic and diarrhoea-associatedEscherichia coli belong to a family of hemagglutinins with Dr receptor recognition. Infect Immun 58: 279–281Google Scholar
  18. 18.
    Swanson TN, Bilge SS, Nowicki B, Moseley SL (1991) Molecular structure of the Dr adhesin: nucleotide sequence and mapping of receptor binding domain by use of fusion constructs. Infect Immun 59: 261–268Google Scholar
  19. 19.
    Rhen A, Elo J, Vaisanen E, Shtonen A, Orskov I, Orskov F, Svenson SB, Makela PH, Krohonen TK (1984) P-fimbriated clones among uropathogenicEscherichia coli strains. Infect Immun 43: 149–155Google Scholar
  20. 20.
    Leffler H, Svanborg-Eden C (1981) Glycolipid receptors for uropathogenicEscherichia coli on human erythrocytes and uroepithelial cells. Infect Immun 34: 920–929Google Scholar
  21. 21.
    Vaisanen V, Elo J, Tallgren LG, Sitonen A, Makela PH, Svanborg Eden C, Kallenius G, Svenson SB, Hultberg H, Korhonen T (1972) Mannose-resistant haemagglutination and P antigen recognition are characteristic ofEscherichia coli causing primary pyelonephritis. Lancet II: 1366–1369Google Scholar
  22. 22.
    Kallenius G, Mollby R, Svenson SB, Helin I, Hultberg H, Cedergren B, Winberg J (1981) Occurrence of P-fimbriatedEscherichia coli in urinary tract infections. Lancet II: 1369–1372Google Scholar
  23. 23.
    Hull RA, Gill RE, Hsu P, Minshew BH, Falkow S (1981) Construction and expression of recombinant plasmids encoding type I ord-mannose resistant pili from a urinary tract infectionEscherichia coli isolate. Infect Immun 33: 933–938Google Scholar
  24. 24.
    Normark S, Lark D, Hull R, Norgren M, Baga M, O'Hanley P, Schoolnik G, Falkow S (1983) Genetics of digalactoside-binding adhesin from a uropathogenicEscherichia coli strain. Infect Immun 41: 942–949Google Scholar
  25. 25.
    Norgren M, Normark S, Lark D, O'Hanley P, Schoolnik G, Falkow S, Svanborg Eden C, Baga M, Uhlin BE (1984) Mutations inE. coli cistrons affecting adhesion to human cells do not abolish Pap pili fiber formation. EMBO J 3: 1159–1165Google Scholar
  26. 26.
    Lindberg FP, Lund B, Normark S (1984) Genes of pyelonephritogenicE. coli required for digalactoside-specific agglutination of human cells. EMBO J 3: 1167–1173Google Scholar
  27. 27.
    Norgren M, Baga M, Tennent JM, Normark S (1987) Nucleotide sequence, regulation and functional analysis of thepapC gene required for cell surface localisation of Pap pili of uropathogenicEscherichia coli. Mol Microbiol 1: 169–178Google Scholar
  28. 28.
    Lund B, Lindberg F, Marklund BI, Normark S (1987) The PapG protein is thed-galactopyranosyl-(1–4)--d-galatopyranose-binding adhesin of uropathogenicEscherichia coli. Proc Natl Acad Sci USA 84: 5898–5902Google Scholar
  29. 29.
    Lund B, Marklung BI, Stromberg N, Lindberg F, Karlsson KA, Normark S (1988) UropathogenicEscherichia coli can express serologically identical pili of different receptor binding specificities. Mol Microbiol 2: 255–263Google Scholar
  30. 30.
    Lindberg F, Lund B, Johansson L, Normark S (1987) Localisation of the receptor-binding protein adhesin at the tip of the bacterial pilus. Nature 328: 84–87Google Scholar
  31. 31.
    Hultgren SJ, Lindberg F, Magnusson G, Kihlberg J, Tennent JM, Normark S (1989) The PapG adhesin of uropathogenicEscherichia coli contains separate regions for receptor binding and for the incorporation into the pilus. Proc Natl Acad Sci USA 86: 4357–4361Google Scholar
  32. 32.
    Holmgren A, Branden C-I (1989) Crystal structure of chaperone protein PapD reveals an immunoglobulin fold. Nature 342: 248–251Google Scholar
  33. 33.
    Holmgren A, Kuehn MJ, Branden C-I, Hultgren SJ (1992) Conserved immunoglobulin-like features in a family of periplasmic pilus chaperones in bacteria. EMBO J 11: 1617–1622Google Scholar
  34. 34.
    Kuehn MJ, Normark S, Hultgren SJ (1991) Immunoglobulin-like PapD chaperone caps and uncaps interactive surfaces of nascently translocated pilus subunits. Proc Natl Acad Sci USA 88: 10586–10590Google Scholar
  35. 35.
    Tennent JM, Lindberg F, Normark S (1990) Integrity ofEscherichia coli P pili during biogenesis: properties and role of PapJ. Mol Microbiol 4: 747–758Google Scholar
  36. 36.
    Baga M, Norgren M, Normark S (1987) Biogenesis ofE. coli Pap pili: PapH, a minor pilin subunit involved in cell anchoring and length modulation. Cell 49: 241–251Google Scholar
  37. 37.
    Baga M, Goransson M, Normark S, Uhlin BE (1985) Transcriptional activation of a Pap pilus virulence operon from uropathogenicEscherichia coli. EMBO J 4: 3887–3893Google Scholar
  38. 38.
    O'Hanley P, Low D, Romero I, Lark D, Vosti K, Falkow S, Schoolnik G (1985) Gal-Gal binding and hemolysin phenotypes and genotypes associated with uropathogenicEscherichia coli. N Engl J Med 313: 414–420Google Scholar
  39. 39.
    Plos K, Carter T, Hull S, Hull R, Svanborg Eden C (1990) Frequency and organisation ofpap homologous DNA in relation to clinical origin of uropathogenicEscherichia coli. J Infect Dis 161: 518–524Google Scholar
  40. 40.
    O'Hanley P, Lark D, Falkow S, Schoolnik G (1985) Molecular basis ofEscherichia coli colonization of the upper urinary tract in BALB/c mice. J Clin Invest 75: 347–360Google Scholar
  41. 41.
    Lomberg H, Hellstrom M, Jodal U, Orskov I, Svanborg Eden C (1989) Properties ofE. coli in patients with renal scarring. J Infect Dis 159: 579–582Google Scholar
  42. 42.
    Lomberg H, Hanson LA, Jacobbson B, Jodal U, Leffler H, Svanborg Eden C (1983) Correlation of P blood group, vesicoureteral reflux, and bacterial attachment in patient with recurrent pyelonephritis. N Engl J Med 308: 1189–1192Google Scholar
  43. 43.
    Svanborg Eden C, Freter R, Hagberg L, Hull R, Hull S, Leffier H, Schoolnik G (1982) Inhibition of experimental ascending urinary tract infection by an epithelial cell surface receptor analogue. Nature 298: 560–562Google Scholar
  44. 44.
    Pecha B, Low D, O'Hanley P (1989) Gal-Gal pili vaccines prevent pyelonephritis by piliatedEscherichia coli in a murine model. J Clin Invest 83: 2102–2108Google Scholar
  45. 45.
    Schmidt MA, O'Hanley P, Lark D, Schoolnik GK (1988) Synthetic peptides corresponding to protective epitopes ofEscherichia coli digalactoside-binding pilin prevent infection in a murine pyelonephritis model. Proc Natl Acad Sci USA 85: 1247–1251Google Scholar
  46. 46.
    Lund B, Lindberg F, Normark S (1988) Structure and antigenic properties of the tip-located P pilus proteins of uropathogenicEscherichia coli. J Bacteriol 170: 1887–1894Google Scholar
  47. 47.
    Hoschutzky H, Lottspeich F, Jann K (1989) Isolation and characterisation of the-galactosyl-1,4-galactosyl specific adhesin (P adhe sin) from fimbriatedEscherichia coli. Infect Immun 57: 76–81Google Scholar
  48. 48.
    Andersson P, Engberg I, Lidin-Janson G, Lincoln K, Hull R, Hull S, Svanborg C (1991) Persistence ofEscherichia coli bacteriuria is not determined by bacterial adherence. Infect Immun 59: 2915–2921Google Scholar
  49. 49.
    Linder H, Engberg I, Mattsby Baltzer I, Jann K, Svanborg Eden C (1988) Induction of inflammation byEscherichia coli on the mucosal level: requirement for adherence and endotoxin. Infect Immun 56: 1309–1313Google Scholar

Copyright information

© IPNA 1992

Authors and Affiliations

  • R. John Roche
    • 1
  • E. Richard Moxon
    • 1
  1. 1.Molecular Infectious Diseases Group, Department of Paediatrics, Institute of Molecular MedicineJohn Radcliffe HospitalOxfordUK

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