1887

Chapter 25 : Fimbriae, Signaling, and Host Response to Urinary Tract Infection

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

Fimbriae, Signaling, and Host Response to Urinary Tract Infection, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817619/9781555813239_Chap25-1.gif /docserver/preview/fulltext/10.1128/9781555817619/9781555813239_Chap25-2.gif

Abstract:

This chapter describes the signaling pathways in the urinary tract and their relevance to asymptomatic carriage, acute symptomatic disease, and chronic infection with tissue damage. There is evidence that P fimbriae enhance bacterial virulence by promoting both intestinal colonization and spread to the urinary tract, by promoting the establishment of bacteriuria, by facilitating the establishment of bacteremia, by activating the innate host response, and by resisting neutrophil killing. P fimbriae use glycosphingolipid receptors (GSLs) as primary receptors to adhere to the host cells and use TLR4 as coreceptors in transmembrane signaling and cell activation. The nonfimbriated strain did not induce a host response in either Tlr4 or Tlr4 mice, demonstrating that P fimbriae and Tlr4 both were needed to trigger the innate host response. The fimbriae have been identified as virulence factors in the murine experimental model of urinary tract infection (UTI) and as colonization factors of the large intestine, but a role in virulence is potentially difficult to reconcile with the occurrence of type 1 fimbriae in both virulent and commensal strains. The GSL recognition receptors are essential for P fimbriae to adhere and to recruit TLR4 for signaling. The expression of receptors for P fimbriae reflects the P blood group, since the receptor structures also act as the P blood group of the host.

Citation: Roche N, Bergsten G, Fischer H, Godaly G, Irjala H, Lundstedt A, Samuelsson P, Svensson M, Ragnarsdottir B, Svanborg C. 2005. Fimbriae, Signaling, and Host Response to Urinary Tract Infection, p 379-394. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch25

Key Concept Ranking

Type 1 Fimbriae
0.6829003
Urinary Tract Infections
0.4805937
Surface Receptors
0.40323848
0.6829003
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

The two steps of the host response to uropathogenic Step 1 involves triggering of the epithelial cells, and step 2 involves the neutrophil-dependent clearance of infection.

Citation: Roche N, Bergsten G, Fischer H, Godaly G, Irjala H, Lundstedt A, Samuelsson P, Svensson M, Ragnarsdottir B, Svanborg C. 2005. Fimbriae, Signaling, and Host Response to Urinary Tract Infection, p 379-394. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch25
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Step 1: host response induction. The PapG adhesin of the P fimbriae adheres to GLS receptors bearing the Gal(α1-4)Galβ epitope. Ceramide is released, and TLR4 is recruited. Ultimately, the cells produce cytokines such as IL-6 and IL-8.

Citation: Roche N, Bergsten G, Fischer H, Godaly G, Irjala H, Lundstedt A, Samuelsson P, Svensson M, Ragnarsdottir B, Svanborg C. 2005. Fimbriae, Signaling, and Host Response to Urinary Tract Infection, p 379-394. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch25
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Step 2: effector phase of the innate host defense. Infected epithelial cells express IL-8 receptors on their surface and produce IL-8. Both IL-8 and the IL-8 receptors guide neutrophils across the epithelial barrier into the urine. In the process, infection is cleared.

Citation: Roche N, Bergsten G, Fischer H, Godaly G, Irjala H, Lundstedt A, Samuelsson P, Svensson M, Ragnarsdottir B, Svanborg C. 2005. Fimbriae, Signaling, and Host Response to Urinary Tract Infection, p 379-394. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch25
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

TLR signaling. The adaptor protein MyD88 is used by most TLRs, the probable exception being TLR3. Signaling through TLR4 can occur via MyD88-dependent or MyD88-independent pathways, and TIRAP is needed for MyD88-dependent signaling by TLR2 and TLR4. TLR4 signaling also involves the TRIF/TRAM-dependent but MyD88-independent pathway, which can activate the transcription factors NF-κB interferon regulating factor 3 (IRF-3). Activation of NF-κB or IRF-3 results in the production of IL-6 and IL-8. The TLRs are depicted as dimers, although dimer formation following stimulation has not been confirmed for all TLRs.

Citation: Roche N, Bergsten G, Fischer H, Godaly G, Irjala H, Lundstedt A, Samuelsson P, Svensson M, Ragnarsdottir B, Svanborg C. 2005. Fimbriae, Signaling, and Host Response to Urinary Tract Infection, p 379-394. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch25
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555817619.chap25
1. Abraham, J. M.,, C. S. Freitag,, J. R. M. Clements,, and B. I. Eisentein. 1985. An invertible element of DNA controls phase variation of type 1 fimbriae of Escherichia coli. Proc. Natl. Acad. Sci. USA 82: 5724 5727.
2. Abraham, S. N.,, and A. Michael. 1998. Mast cells and basophils in innate immunity. Semin. Immunol. 10: 373 381.
3. Abreu, M. T.,, P. Vora,, E. Faure,, L. S. Thomas,, E. T. Arnold,, and M. Arditi. 2001. Decreased espression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. J. Immunol. 167: 1609 1616.
4. Agace, W.,, S. Hedges,, U. Andersson,, J. Andersson,, M. Ceska,, and C. Svanborg. 1993. Selective cytokine production by epithelial cells following exposure to Escherichia coli. Infect. Immun. 61: 602 609.
5. Agace, W. W.,, S. R. Hedges,, M. Ceska,, and C. Svanborg. 1993. Interleukin-8 and the neutrophil response to mucosal gram-negative infection. J. Clin. Investig. 92: 780 785.
6. Anderson, P.,, I. Engberg,, G. Lidin-Janson,, K. Lincoln,, R. Hull,, S. Hull,, and C. Svanborg. 1991 Persistence of Escherichia coli bacteriuria is not determined by bacterial adherence. Infect. Immun. 59: 2915 2921.
7. Anderson, K. V.,, L. Bokla,, and C. Nusslein-Volhard. 1985. Establishment of the dorsal-ventral polarity in the Drosophilia embryo: the induction of polarity by the Toll gene product. Cell 42: 791 798.
8. Bäckhed, F.,, M. Soderhall,, P. Ekman,, S. Normark,, and A. Richter-Dahlfors. 2001. Induction of the innate immune responses by Escherichia coli and purified lipopolysaccharide correlate with organ- and cell-specific expression of Toll-like receptors within the human urinary tract. Cell. Microbiol. 3: 153 158.
9. Bäckhed, F.,, L. Meijer,, S. Normark,, and A. Richter-Dahlfors. 2002. TLR4-dependent recognition of lipopolysaccharide by epithelial cells requires sCD14. Cell. Microbiol. 4: 493 501.
10. Bäckhed, F.,, S. Normark,, E. K. H. Schweda,, S. Oscarsson,, and A. Richter-Dahlfors. 2003. Structural requirements for TLR4-mediated LPS signaling: A biological role for LPS modifications. Microbes Infect. 5: 1057 1063.
11. Baggiolini, M.,, B. Dewald,, and B. Moser. 1994. Interleukin- 8 and related chemotactic cytokines—CXC and CC chemokines. Adv. Immunol. 55: 97 179.
12. Bahrani-Mougeot, F. K.,, E. L. Buckles,, C. V. Lockatell,, J. R. Hebel,, D. E. Johnson,, C. M. Tang,, and M. S. Donnenberg. 2002. Type 1 fimbriae and extracellular polysaccharides are preeminent Escherichia coli virulence determinants in the murine urinary tract. Mol. Microbiol. 45: 1079 1093.
13. Baorto, D. M.,, Z. Gao,, R. Malaviya,, M. L. Dustin,, A. van der Merwe,, D. M. Lublin,, and S. N. Abraham. 1997. Survival of FimH-expressing enterobacteria in macrophages relies on glycolipid traffic. Nature 389: 636 639.
14. Bar-Shavit, Z.,, I. Ofek,, G. Goldman, Mirelman D, and N. Sharon. 1977. Mannose residues on phagocytes as receptors for the attachment of Escherichia coli and Salmonella typhi. Biochem. Biophys. Res. Commun. 78: 455 460.
15. Bergsten, G.,, M. Samuelsson,, B. Wullt,, I. Leijonhufvud,, H. Fischer,, and C. Svanborg. 2004. PapG dependent adhesion breaks mucosal inertia and triggers the innate host response. J. Infect. Dis. 189: 1734 1742.
16. Blomfield, I.,, and M. van der Woude,. 2002. Regulation and function of phase variation in Escherichia coli, p. 89 113. In M. Wilson (ed.), Bacterial Adhesion to Host Tissues: Mechanisms and Consequences, vol. 1. Cambridge University Press, Cambridge, United Kingdom.
17. Blomfield, I. C.,, D. H. Kulasekara,, and B. I. Eisenstein. 1997. Integration host factor stimulates both FimB- and FimE-mediated site-specific DNA inversion that controls phase variation of type 1 fimbriae expression in Escherichia coli. Mol. Microbiol. 23: 705 717.
18. Blomfield, I. C.,, P. J. Calie,, K. J. Eberhardt,, M. S. McClain,, and B. I. Eisenstein. 1993. lrp stimulates phase variation of type 1 fimbriation in Escherichia coli K-12. J. Bacteriol. 175: 27 36.
19. Bock, K.,, M. E. Breimer,, A. Brignole,, G. C. Hansson,, K.-A. Karlsson,, G. Larson,, H. Leffler,, B. E. Samuelsson,, N. Strömberg,, C. Svanborg-Edén,, and J. Thurin. 1985. Specificity of binding of a strain of Escherichia coli to Gal alpha 1-4 Gal containing glycosphingolipids. J. Biol. Chem. 260: 8545 8551.
20. Brinton, C. 1965. The structure, function, synthesis, and genetic control of bacterial pili, and a molecular model of DNA and RNA transport in gram-negative bacteria. Trans. N.Y. Acad. Sci. 27: 1003 1054.
21. Bussolati, B.,, S. David,, V. Cambi,, P. S. Tobias,, and G. Camussi. 2002. Urinary soluble CD14 mediates human proximal tubular epithelial cell injury induced by LPS. Int. J. Mol. Med. 10: 441 449.
22. Cacalano, G.,, J. Lee,, K. Kikly,, A. M. Ryan,, S. Pitts-Meek,, B. Hultgren,, W. I. Wood,, and K. W. Moore. 1994. Neutrophil and B cell expansion in mice that lack the murine IL- 8 receptor homolog. Science 265: 682 684.
23. Condron, C.,, D. Toomey,, R. G. Casey,, M. Shaffii,, T. Creagh,, and D. Bouchier-Hayes. 2003. Neutrophil bacterial function is defective in patients with recurrent urinary tract infections. Urol. Res. 31: 329 334.
24. Connell, I.,, W. Agace,, P. Klemm,, M. Schembri,, S. Marild,, and C. Svanborg. 1996. Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract. Proc. Natl. Acad. Sci. USA 93: 9827 9832.
25. de Man, P.,, C. van Kooten,, L. Aarden,, I. Engberg,, H. Linder,, and C. Svanborg Edén. 1989. Interleukin-6 induced at mucosal surfaces by gram-negative bacterial infection. Infect. Immun. 57: 3383 3388.
26. Dobrindt, U.,, F. Agerer,, K. Michaelis,, A. Janka,, C. Buchrieser,, M. Samuelsson,, C. Svanborg,, G. Gottschalk,, H. Karch,, and J. Hacker. 2003. Analysis of genome plasticity in pathogenic and commensal Escherichia coli isolates by use of DNA arrays. J. Bacteriol. 185: 1831 1840.
27. Dodson, K. W.,, J. S. Pinkner,, T. Rose,, G. Magnusson,, S. J., Hultgren,, and G. Waksman. 2001. Structural basis of the interaction of the pyelonephritic E. coli adhesin to its kidney receptor. Cell 105: 733 743.
28. Donnenberg, M. S.,, and R. A. Welsh,. 1996. Virulence determinants of uropathogenic Escherichia coli, p. 135 174. In H. L. T. Mobley, and J. W. Warren (ed.), Urinary Tract Infections: Molecular Pathogenesis and Clinical Management. ASM Press, Washington, D.C.
29. Duguid, J.,, I. Smith,, G. Dempster,, and P. Edmunds. 1955. Non-flagellar filamentous appendages (“fimbriae”) and haemagglutinating activity in Bacterium coli. J. Pathol. Bacteriol. 70: 335 348.
30. Esposito, D.,, and J. J. Scocca. 1997. The integrase family of tyrosine recombinases: evolution of a conserved active site domain. Nucleic Acids Res. 25: 3605 3614.
31. Frendéus, B.,, G. Godaly,, L. Hang,, D. Karpman,, A. C. Lundstedt,, and C. Svanborg. 2000. Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart. J. Exp. Med. 192: 881 890.
32. Frendéus, B.,, C. Wachtler,, M. Hedlund,, H. Fischer,, P. Samuelsson,, M. Svensson,, and C. Svanborg. 2001. Escherichia coli P fimbriae utilize the Toll-like receptor 4 pathway for cell activation. Mol. Microbiol. 40: 37 51.
33. Frendéus, B.,, G. Godaly,, L. Hang,, D. Karpman,, and C. Svanborg. 2001. Interleukin-8 receptor deficiency confers susceptibility to acute pyelonephritis. J. Infect. Dis. 183( Suppl. 1): S56 S60.
34. Gally, D. L.,, J. Leathart,, and I. C. Blomfield. 1996. Interaction of FimB and FimE with the fim switch that controls the phase variation of type 1 fimbriae in Escherichia coli K-12. Mol. Microbiol. 21: 725 738.
35. Giampapa, C. S.,, S. N. Abraham,, T. M. Chiang,, and E. H. Beachey. 1988. Isolation and characterization of a receptor for type 1 fimbriae of Escherichia coli from guinea pig erythrocytes. J. Biol. Chem. 263: 5362 5367.
36. Godaly, G.,, B. Frendéus,, A. Proudfoot,, M. Svensson,, P. Klemm,, and C. Svanborg. 1998. Role of fimbriae-mediated adherence for neutrophil migration across Escherichia coli-infected epithelial cell layers. Mol. Microbiol. 30: 725 735.
37. Godaly, G.,, A. E. Proudfoot,, R. E. Offord,, C. Svanborg,, and W. W. Agace. 1997. Role of epithelial interleukin-8 (IL-8) and neutrophil IL-8 receptor A in Escherichia coli-induced transuroepithelial neutrophil migration. Infect. Immun. 65: 3451 3456.
38. Godaly, G.,, L. Hang,, B. Frendéus,, and C. Svanborg. 2000. Transepithelial neutrophil migration is CXCR1 dependent in vitro and is defective in IL-8 receptor knockout mice. J. Immunol. 165: 5287 5294.
39. Godaly, G.,, G. Bergsten,, L. Hang,, H. Fischer,, B. Frendéus,, A.-C. Lundstedt,, M. Samuelsson,, P. Samuelsson,, and C. Svanborg. 2001. Neutrophil recruitment, chemokine receptors, and resistance to mucosal infection. J. Leukoc. Biol. 69: 899 906.
40. Hacker, J.,, L. Bender,, M. Ott,, J. Wingender,, B. Lund,, R. Marre,, and W. Goebel. 1990. Deletions of chromosomal regions coding for fimbriae and hemolysins occur in vitro and in vivo in various extraintestinal Escherichia coli isolates. Microb. Pathog. 8: 213 225.
41. Hacker, J.,, G. Blum-Oehler,, I. Muhldorfer,, and H. Tschape. 1997. Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution. Mol. Microbiol. 23: 1089 1097.
42. Hagberg, L.,, R. Hull,, S. Hull,, J. R. McGhee,, S. M. Michalek,, and C. Svanborg-Edén. 1984. Differences in the susceptibility to gram-negative urinary tract infection between C3H/HeJ and C3H/HeN mice. Infect. Immun. 46: 839 844.
43. Hagberg, L.,, U. Jodal,, T. K. Korhonen,, G. Lidin-Janson,, U. Lindberg,, and C. Svanborg-Edén. 1981. Adhesion, hemagglutination, and virulence of Escherichia coli causing urinary tract infections. Infect. Immun. 31: 564 570.
44. Hagberg, L.,, R. Hull,, S. Falkow,, R. Freter,, and C. Svanborg- Edén. 1983. Contribution of adhesion to bacterial persistence in the mouse urinary tract. Infect. Immun. 40: 265 272.
45. Hang, L.,, M. Haraoka,, W. W. Agace,, H. Leffler,, M. Burdick,, R. Strieter,, and C. Svanborg. 1999. Macrophage inflammatory protein-2 is required for neutrophil passage across the epithelial barrier of the infected urinary tract. J. Immunol. 162: 3037 3044.
46. Hang, L.,, B. Frendéus,, G. Godaly,, and C. Svanborg. 2000. Interleukin-8 receptor knockout mice have subepithelial entrapment and renal scarring following acute pyelonephritis. J. Infect. Dis. 182: 1738 1748.
47. Hang, L.,, B. Wullt,, Z. Shen,, D. Karpman,, and C. Svanborg. 1998. Cytokine repertoire of epithelial cells lining the human urinary tract. J. Urol. 159: 2185 2192.
48. Hannun, Y. A. 1994. The sphingomyelin cycle and the second messenger function of ceramide. J. Biol. Chem. 269: 3125 3128.
49. Hanson, M. S.,, and C. C. Brinton, Jr. 1988. Identification and characterization of E. coli type 1 pilus tip adhesion protein. Nature 332: 265 268.
50. Haraoka, M.,, L. Hang,, W. Agace,, M. Burdick,, R. Strieter,, and C. Svanborg. 1999. Neutrophil recruitment and resistance to mucosal bacterial infection. J. Infect. Dis. 180: 1220 1229.
51. Hashimoto, C.,, K. L. Hudson,, and K. V. Anderson. 1988. The Toll gene of Drosophilia, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein. Cell 52: 269 279.
52. Hedges, S.,, P. Anderson,, G. Lidin-Janson,, P. de Man,, and C. Svanborg. 1991. Interleukin-6 response to deliberate colonization of the human urinary tract with gram-negative bacteria. Infect. Immun. 59: 421 427.
53. Hedges, S.,, M. Svensson,, and C. Svanborg. 1992. Interleukin- 6 response of epithelial cell lines to bacterial stimulation in vitro. Infect. Immun. 60: 1295 1301.
54. Hedlund, M.,, B. Frendéus,, C. Wachtler,, L. Hang,, H. Fischer,, and C. Svanborg. 2001. Type 1 fimbriae deliver an LPS- and TLR4-dependent activation signal to CD14-negative cells. Mol. Microbiol. 39: 542 552.
55. Hedlund, M.,, C. Wachtler,, E. Johansson,, L. Hang,, J. E. Sommerville,, R. P. Darveau,, and C. Svanborg. 1999. P fimbriae-dependent, lipopolysaccharide-independent activation of epithelial cytokine responses. Mol. Microbiol. 33: 693 703.
56. Hedlund, M.,, M. Svensson, Å. Nilsson, R.-D. Duan, and C. Svanborg. 1996. Role of the ceramide signaling pathway in cells exposed to P fimbriated Escherichia coli. J. Exp. Med. 183: 1037 1044.
57. Hedlund, M., Å. Nilsson, R.-D. Duan, and C. Svanborg. 1998. Sphingomyelin, glycosphingolipids and ceramide signaling in cells exposed to P-fimbriated Escherichia coli. Mol. Microbiol. 29: 1297 1306.
58. Hornef, M. W.,, T. Frisan,, A. Vandewalle,, S. Normark,, and A. Richter-Dahlfors. 2002. Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in the intestinal epithelial cells. J. Exp. Med. 195: 559 570.
59. Hornung, V.,, S. Rothenfusser,, S. Britsch,, A. Krug,, B. Jahrsdorfer,, T. Giese,, S. Endres,, and G. Hartman. 2002. Quantitive expression of Toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol. 168: 4531 4537.
60. Hull, R. A.,, R. E. Gill,, P. Hsu,, B. H. Minshew,, and S. Falkow. 1981. Construction and expression of recombinant plasmids encoding type 1 or D-mannose-resistant pili from a urinary tract infection. Infect. Immun. 33: 933 938.
61. Hultgren S. J.,, S. Abraham,, M. Caparon,, P. Falk,, J. W. St Geme III,, and S. Normark. 1993. Pilus and nonpilus bacterial adhesins; assembley and function in cell recognition. Cell 73: 887 901.
62. Jacob-Dubuisson, F.,, J. Heuser,, K. Dodson,, S. Normark,, and S. Hultgren. 1993. Initiation of assembly and association of the structural elements of a bacterial pilus depend on two specialized tip proteins. EMBO J. 12: 837 847.
63. Johnson, G. B.,, G. J. Brunn,, Y. Kodaira,, and J. L Platt. 2002. Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J. Immunol. 168: 5233 5239.
64. Johnson, J. 1991. Virulence factors in Escherichia coli urinary tract infection. Clin. Microbiol Rev. 4: 80 128.
65. Jones, C. H.,, K. Dodson,, and S. Hultgren,. 1996. Structure, function, and assembly of adhesive P pili, p. 175 219. In L. T. H. Mobley, and J. Warren (ed.), Urinary Tract Infections: Molecular Pathogenesis and Clinical Management. ASM Press, Washington, D.C.
66. Kaijser, B.,, L. A. Hanson,, U. Jodal,, G. Lidin-Janson,, and J. B. Robbins. 1977. Frequency of E. coli K antigens in urinary-tract infections in children. Lancet i: 663 666.
67. Kass, E. H. 1956. Asymptomatic infections in the urinary tract. Trans. Assoc. Am. Physicians 69: 56 64.
68.Klemm. P. 1986. Two regulatory fim genes, fimB and fimE, control the phase variation of type 1 fimbriae of Escherichia coli. EMBO J. 5: 13891393.
69. Krogfelt, K. A.,, and P. Klem. 1988. Investigation of minor components of Escherichia coli type 1 fimbria: protein, chemical and immunological aspects. Microb. Pathog. 4: 231 238.
70. Krogfelt, K. A.,, H. Bergmans,, and P. Klemm. 1990. Direct evidence that the FimH protein is the mannose-specific adhesin of Escherichia coli type 1 fimbriae. Infect. Immun. 58: 1995 1998.
71. Kuehn, M. J.,, J. Heuser,, S. Normark,, and S. J. Hultgren. 1992. P pili in Escherichia coli are composite fibers with distinct fibrillar adhesive tips. Nature 356: 252 255.
72. Kukkonen, M.,, T. Raunio,, R. Virkola,, K. Lahteenmaki,, P. H. Makela,, P. Klemm,, S. Clegg,, and T. K. Korhonen. 1993. Basement membrane carbohydrate as a target for bacterial adhesion: binding of type 1 fimbriae of Salmonella enterica and Escherichia coli to laminin. Mol. Microbiol. 7: 229 237.
73. Kunin, C. 1987. Urinary Tract Infections. Detection, Prevention and Management, 5th ed. The Williams & Wilkins Co., Baltimore, Md.
74. Lanne, B.,, B. M. Olsson,, P. A. Jovall,, J. Ångström,, H. Linder,, B. I. Marklund,, J. Bergström,, and K.-A. Karlsson. 1995. Glycoconjugate receptors for P-fimbriated Escherichia coli in the mouse: an animal model of urinary tract infection. J. Biol. Chem. 270: 9017 9025.
75. Leffler, H.,, and C. Svanborg-Edén. 1980. Chemical identification of a glycosphingolipid receptor for Escherichia coli attaching to human urinary tract epithelial cells and agglutinating human erythrocytes. FEMS Microbiol. Lett. 8: 127 134.
76. Leffler, H.,, and C. Svanborg-Edén. 1981. Glycolipid receptors for Escherichia coli on human erythrocytes and uroepithelial cells. Infect. Immun. 34: 920 929.
77. Lemaitre, B.,, E. Nicolas,, L. Michaut,, J. M. Reichhart,, and J. A. Hoffmann. 1996. The dorso-ventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86: 973 983.
78. Levin, B. R.,, and C. Svanborg. 1990. Selection and evolution of virulence in bacteria: an ecumenical excursion and modest suggestion. Parasitology 100(Suppl.): S103 S115.
79. Lindberg, F.,, B. Lund,, L. Johansson,, and S. Normark. 1987. Localization of the receptor binding protein adhesin at the tip of the bacterial pilus. Nature 328: 84 87.
80. Lindberg, U. 1975. Asymptomatic bacteriuria in school girls. V. The clinical course and response to treatment. Acta Paediatr. Scand. 64: 718 724.
81. Lindstedt, R.,, G. Larson,, P. Falk,, U. Jodal,, H. Leffler,, and C. Svanborg-Edén. 1991. The receptor repertoire defines the host range for attaching Escherichia coli recognizing globo- A. Infect. Immun. 59: 1086 1092.
82. Lomberg, H.,, U. Jodal,, C. Svanborg Eden,, H. Leffler,, and B. Samuelsson. 1981. P 1 blood group and urinary tract infection. Lancet i: 551 552.
83. Mabeck, C. E.,, F. Orskov,, and I. Orskov. 1971. Escherichia coli serotypes and renal involvement in urinary-tract infection. Lancet i: 1312 1314.
84. Marcus, D. M.,, M. Naiki,, and S. K. Kundu. 1976. Abnormalities in the glycosphingolipid content of human P k and p erythrocytes. Proc. Natl. Acad. Sci. USA 73: 3263 3267.
85. Martinez, J. J.,, M. A. Mulvey,, J. D. Schilling,, J. S. Pinkner,, and J. S. Hultgren. 2000. Type 1 pilus-mediated bacterial invasion of the bladder epithelial cells. EMBO J. 19: 2803 2812.
86. Mobley, H. L.,, K. G. Jarvis,, J. P. Elwood,, D. I. Whittle,, C. V. Lockatell,, R. G. Russell,, D. E. Johson,, M. S. Donnenberg,, and J. Warren. 1993. Isogenic P-fimbrial deletion mutation of pyelonephritogenic Escherichia coli: the role of alpha Gal(1-4) beta Gal binding in virulence of a wild type strain. Mol. Microbiol. 10: 143 155.
87. Mulvey, M. A.,, J. D. Schilling,, and S. J. Hultgren. 2001. Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection. Infect. Immun. 69: 4572 4579.
88. Muzio, M.,, D. Bosisio,, N. Polentarutti,, G. D’Amico,, A. Stoppacciaro,, R. Mancinelli,, C. van’t Veer,, G. Penton-Rol,, L. P. Ruco,, P. Allavena,, and A. Mantovani. 2000. Differential expression and regulation of Toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J. Immunol. 164: 5998 6004.
89. Nagai, Y.,, S. Akashi,, M. Nagafuku,, M. Ogata,, Y. Iwakura,, S. Akira,, T. Kitamura,, A. Kosugi,, M. Kimoto,, and K. Miyake. 2002. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat. Immunol. 3: 667 672.
90. Nordenstam, G. R.,, C. A. Brandenberg,, A. S. Oden,, C. M. Svanborg-Edén,, and A. Svanborg. 1986. Bacteriuria and mortality in an elderly population. N. Engl. J. Med. 314: 1152 1156.
91.Nowicki, B, C. Svanborg-Edén, R. Hull, and S. Hull. 1989. Molecular analysis and epidemiology of the Dr hemagglutinin of Escherichia coli. Infect. Immun. 57: 446451.
92. O’Hanley, P.,, D. Lark,, S. Falkow,, and G. Schoolnik. 1985. Molecular basis of Escherichia coli colonization of the upper urinary tract in BALB/c Mice. J. Clin. Investig. 75: 347 360.
93. Ohashi, K.,, V. Burkart,, S. Flohe,, and H. Kolb. 2000. Cutting edge. Heat shock protein 60 is a putative endogenous ligand of the Toll-like receptor-4 complex. J. Immunol. 164: 558 561.
94. Ohman, L.,, K. E. Magnusson,, and O. Stendahl. 1985. Mannose- specific and hydrophobic interaction between Escherichia coli and polymorphonuclear leukocytes—influence of bacterial culture period. Acta Pathol. Microbiol. Immunol. Scand Ser. B 93: 125 131.
95. Okamura, Y.,, M. Watari,, E. S. Jerud,, D. W. Young,, S. T. Ishizaka,, J. Rose,, J. C. Chow,, and J. F. Strauss III. 2001. The extra domain A of fibronectin activates Toll-like receptor 4. J. Biol. Chem. 276: 10229 10233.
96. Olsen, P. B.,, and P. Klemm. 1994. Localisation of promoters in the fim gene cluster and the effect of H-NS on the transcription of fimB and fimE. FEMS Microbiol. Lett. 116: 95 100.
97. Olsen, P. B.,, M. A. Schembri,, D. L. Gally,, and P. Klemm. 1998. Differential temperature modulation by H-NS of the fimB and fimE recombinase genes, which control the orientation of the type 1 fimbrial switch. FEMS Microbiol. Lett. 162: 17 23.
98. Orskov, I.,, C. Svanborg Edén,, and F. Orskov. 1988. Aerobactin production of serotyped Escherichia coli from urinary tract infections. Med. Microbiol. Immunol. 177: 9 14.
99. Orskov, I.,, A. Ferencz,, and F. Orskov. 1980. Tamm-Horsfall protein or uromucoid is the normal urinary slime that traps type 1 fimbriated Escherichia coli. Lancet i: 887.
100. Otega-Cava, C. F.,, S. Ishihara,, M. A. Rumi,, K. Kawashima,, N. Ishimura,, H. Kazumori,, J. Udagawa,, Y. Kadowaki,, and Y. Kinoshita. 2003. Strategic compartmentalization of Toll-like receptor 4 in the mouse gut. J. Immunol. 170: 3977 3985.
101. Pak, J.,, Y. Pu,, Z. T. Zhang,, D. L. Hasty,, and X. R. Wu. 2001. Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli from binding to uroplakin 1a and 1b receptors. J. Biol. Chem. 276: 9924 9930.
102. Plos, K,, H. Connell,, U. Jodal,, B. I. Markund,, S. Marild,, B. Wettergren,, and C. Svanborg. 1995. Intestinal carriage of P fimbriated Escherichia coli and the susceptibility to urinary tract infection in young children. J. Infect. Dis. 171: 625 631.
103. Plos, K.,, T. Carter,, S. Hull,, and C. Svanborg-Edén. 1990. Frequency and organization of pap homologous DNA in relation to clinical origin of Escherichia coli. J. Infect. Dis. 161: 518 524.
104. Poltorak, A.,, X. He,, I. Smirnova,, M. Y. Liu,, C. V. Huffel,, X. Du,, D. Birdwell,, E. Alejos,, M. Silva,, C. Galanos,, M. Freudenberg,, P. Ricciardi-Castagnoli,, B. Layton,, and B. Beutler. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in the tlr4 gene. Science 282: 2085 2088.
105. Pouttu, R.,, T. Puustinen,, R. Virkola,, J. Hacker,, P. Klemm,, and T. K. Korhonen. 1999. Amino acid residue Ala-62 in the FimH fimbrial adhesin is critical for the adhesiveness of meningitis associated Escherichia coli to collagens. Mol. Microbiol. 31: 1747 1757.
106. Qureshi, S.T.,, L. Lariviere,, G. Leveque,, K. J. Moore,, P. Gros,, and D. Malo. 1999. Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J. Exp. Med. 189: 615 625.
107. Rock, F. L.,, G. Hardiman,, J. C. Timans,, R. A. Kastelein,, and J. F. Bazan. 1998. A family of human receptors structurally related to Drosophila Toll. Proc. Natl. Acad. Sci. USA 95: 588 593.
108. Rosetto, M.,, Y. Engstrom,, C. T. Baldari,, J. L. Telford,, and D. Hultmark. 1995. Signals from the IL-1 receptor homolog, Toll, can activate an immune response in a Drosophila hemocyte cell line. Biochem. Biophys. Res. Commun. 209: 111 116.
109. Samuelsson, P.,, L. Hang,, B. Wullt,, H. Irjala,, and C. Svanborg. 2004. Expression and cytokine response in the human urinary tract mucosa. Infect. Immun. 72: 3179 3186.
110. Schembri, M. A.,, D. W. Ussery,, C. Workman,, H. Hasman,, and P. Klemm. 2002. DNA microarray analysis of fim mutations in Escherichia coli. Mol. Genet. Genomics 267: 721 729.
111. Schembri, M. A.,, P. B. Olsen,, and P. Klemm. 1998. Orientation- dependent enhancement by H-NS of the activity of the type 1 fimbrial phase switch promoter in Escherichia coli. Mol. Gen. Genet. 259: 336 344.
112. Schilling, J. D.,, S. M. Martin,, D. A. Hunstad,, K. P. Patel,, M. A. Mulvey,, S. S. Justice,, R. G. Lorenz,, and S. J. Hultgren. 2003. CD14- and Toll-like receptor-dependent activation of bladder epithelial cells by lipopolysaccharide and type 1 piliated Escherichia coli. Infect. Immun. 71: 1470 1480.
113. Shahin, R. D.,, I. Engberg,, L. Hagberg,, and C. S. Svanborg. 1987. Neutrophil recruitment and bacterial clearance correlated with LPS responsiveness in local gram-negative infection. J. Immunol. 138: 3475 3480.
114. Sharon, N.,, Y. Eshdat,, J. Silverblatt,, and I. Ofek. 1981. Bacterial adherence to cell surface sugars. Ciba Found. Symp. 80: 119 141.
115. Sharon, N. 1987. Bacterial lectins, cell-cell recognition and infectious disease. FEBS Lett. 217: 145 157.
116. Shimazu, R.,, S. Akashi,, H. Ogata,, Y. Nagai,, K. Fukudome,, K. Miyake,, and M. Kimoto. 1999. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189: 1777 1782.
117. Smiley, S. T.,, J. A. King,, and W. W. Hancoock. 2001. Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J. Immunol. 167: 2887 2894.
118. Sokurenko, E. V.,, H. S. Courtney,, J. Maslow,, A. Siitonen,, and D. L Hasty. 1995. Quantitative differences in adhesiveness of type 1 fimbriated Escherichia coli due to structural differences in fimH genes. J. Bacteriol. 177: 3680 3686.
119. Sokurenko, E. V.,, H. S. Courtney,, D. E. Ohman,, P. Klemm,, and D. L. Hasty. 1994. FimH family of type 1 fimbrial adhesins: functional heterogeneity due to minor sequence variations among fimH genes. J. Bacteriol. 176: 748 755.
120. Sommerville, J. E. J.,, L. Cassiano,, B. Bainbridge,, M. D. Cunningham,, and R. P. Darveau. 1996. A novel Escherichia coli lipid A mutant that produces an anti-inflammatory lipopolysaccharide. J. Clin. Investig. 97: 359 365.
121. Spears, P. A.,, D. Schauer,, and P. E. Orndorff. 1986. Metastable regulation of type 1 piliation in Escherichia coli and isolation and characterization of a phenotypically stable mutant. J. Bacteriol. 168: 179 185.
122. Stamm, W. E.,, M. McKevitt,, P. L. Roberts,, and N. J. White. 1991. Natural history of recurrent urinary tract infections in women. Rev. Infect. Dis. 13: 77 84.
123. Stamm, W. E.,, and S. R. Norrby. 2001. Urinary tract infections: disease panorama and challenges. J. Infect. Dis. 183( Suppl. 1): S1 S4.
124. Stenqvist, K.,, T. Sandberg,, G. Lidin-Janson,, F. Orskov,, I. Orskov,, and C. Svanborg-Edén. 1987. Virulence factors of Escherichia coli in urinary isolates from pregnant women. J. Infect. Dis. 156: 870 877.
125. Svanborg, C.,, G. Bergsten,, H. Fischer,, B. Frendéus,, G. Godaly,, E. Gustafsson,, L. Hang,, M. Hedlund,, D. Karpman,, A. C. Lundstedt,, M. Samuelsson,, P. Samuelsson,, M. Svensson,, and B. Wullt. 2001. The “innate” host response protects and damages the infected urinary tract. Ann. Med. 33: 563 570.
126. Svanborg, C.,, G. Bergsten,, H. Fischer,, B. Frendéus,, G. Godaly,, E. Gustafsson,, L. Hang,, M. Hedlund,, A. C. Lundstedt,, M. Samuelsson,, P. Samuelsson,, M. Svensson,, and B. Wullt,. 2002. Adhesion, signal transduction and mucosal inflammation, p. 223 240. In M. Wilson (ed.), Bacterial Adhesion to Host Tissues, vol. 1. Cambridge University Press, Cambridge, United Kingdom.
127. Svanborg-Edén, C.,, L. A. Hanson,, U. Jodal,, U. Lindberg,, and A. S. Åkerlund. 1976. Variable adherence to normal human urinary-tract epithelial cells of Escherichia coli strains associated with various forms of urinary-tract infection. Lancet i: 490 492.
128. Svanborg-Edén, C.,, B. Eriksson,, and L. A. Hanson. 1977. Adhesion of Escherichia coli to human uroepithelial cells in vitro. Infect. Immun. 18: 767 774.
129. Svanborg-Edén, C.,, L.-M. Bjursten,, R. Hull,, S. Hull,, K.-E. Magnusson,, Z. Moldovano,, and H. Leffler. 1984. Influence of adhesins on the interaction of Escherichia coli with human phagocytes. Infect. Immun. 44: 672 680.
130. Svanborg-Edén, C.,, L. Hagberg,, L. A. Hanson,, S. Hull,, R. Hull,, U. Jodal,, H. Leffler,, H. Lomberg,, and E. Strobe. 1983. Bacterial adherence—a pathogenic mechanism in urinary tract infections caused by Escherichia coli. Prog. Allergy 33: 175 188.
131. Svanborg-Edén, C.,, R. Freter,, L. Hagberg,, R. Hull,, H. Leffler,, and G. Schoolnik. 1982. Inhibition of experimental ascending urinary tract infection by epithelial cell-surface receptor analogue. Nature 298: 560 562.
132. Svanborg-Edén, C.,, L. Hagberg,, R. Hull,, K.-E. Magnusson,, and L. Öhman. 1987. Bacterial virulence verus host resistance in the urinary tracts of mice. Infect. Immun. 55: 1224 1232.
133. Svensson, M.,, B. Frendéus,, T. Butters,, F. Platt,, R. Dwek,, and C. Svanborg. 2003. Glycolipid depletion in antimicrobial therapy. Mol. Microbiol. 47: 453 461.
134. Takeda, K.,, T. Kaisho,, and S. Akira. 2003. Toll-like receptors. Annu. Rev. Immunol. 21: 335 376.
135. Termeer, C.,, F. Benedix,, J. Sleeman,, C. Fieber,, U. Voith,, T. Ahrens,, K. Miyake,, M. Freudenberg,, C. Galanos,, and J. C. Simon. 2002. Oligosaccharides of hyaluronan activate dendritic cells via Toll-like receptor 4. J. Exp. Med. 195: 99 111.
136. Tewari, R.,, T. Ikeda,, R. Malaviya,, J. I. MacGregor,, J. R. Little,, S. J. Hultgren,, and S. N. Abraham. 1994. The papG tip adhesin of P fimbriae protects Escherichia coli from neutrophil bacterial activity. Infect. Immun. 62: 5296 5304.
137. Vabulas, R. M.,, P. Ahmad-Nejad,, C. de Costa,, T. Miethke,, C. J. Kirschning,, H. Hacker,, and H. Wagner. 2001. Endocytosed HSP60s use Toll-like receptor 2 (TLR2) and TLR4 to activate the Toll/interleukin-1 receptor signaling pathway in innate immune cells. J. Biol. Chem. 276: 31332 31339.
138. Vabulas, R.M.,, P. Ahmad-Nejad,, S. Ghose,, C. J. Kirschning,, R. D. Issels,, and H. Wagner. 2002. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J. Biol. Chem. 277: 15107 15112.
139. Väisanen, V.,, J. Elo,, L. G. Tallgren,, A. Siitonen,, P. H. Mäkelä,, C. Svanborg-Edén,, G. Källenius,, S. B. Svensson,, H. Hultberg,, and T. Korhonen. 1981. Mannose-resistant haemagglutination and P antigen recognition are characteristic of Escherichia coli causing primary pyelonephritis. Lancet i: 1366 1369.
140. Vaisanen-Rhen, V.,, J. Elo,, E. Vaisanen,, A. Siitonen,, I. Orskov,, F. Orskov,, S. B., Svensson,, P. H. Makela,, and T. K. Korhonen. 1984. P-fimbriated clones among Escherichia coli strains. Infect. Immun. 43: 149 155.
141. Virkola, R.,, B. Westerlund,, H. Holthofer,, J. Parkkinen,, M. Kekomaki,, and T. K. Korhonen. 1988. Binding characteristics of Escherichia coli adhesins in human urinary bladder. Infect. Immun. 56: 2615 2622.
142. Visintin, A.,, A. Mazzoni,, J. A. Spitzer,, and D. M. Segal. 2001. Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4. Proc. Natl. Acad. Sci. USA 98: 12156 12161.
143. Warren, J. W.,, H. L. Mobley,, and A. L. Trifillis. 1988. Internalization of Escherichia coli into human renal tubular epithelial cells. J. Infect. Dis. 158: 221 223.
144. Walz, W.,, M. A. Schmidt,, A. F. Labigne-Roussel,, S. Falkow,, and G. Schoolnik. 1985. AFA-1, a cloned afimbrial X-type adhesin from a human pyelonephritic Escherichia coli strains. Purification and chemical, functional and serological characterization. Eur. J. Biochem. 152: 315 321.
145. Welsh, R. A.,, P. Shahaireen,, D. Robbins,, W. F. Keene,, G. Gekker,, and P. R. Peterson,. 1989. Epidiemiologic observations involving the Escherichia coli hemolysin p. 136 143. In E. H. Kass, and C. Svanborg-Edén (ed.), Host-Parasite Interactions in the Urinary Tract. The University of Chicago Press Ltd., London, United Kingdom.
146. Wold, A. E.,, M. Thorssén,, S. Hull,, and C. Svanborg-Edén. 1988. Attachment of Escherichia coli via mannose or Galα1- 4Galβ-containing receptors to human colonic epithelial cells. Infect. Immun. 56: 2531 2537.
147. Wold, A. E.,, J. Mestecky,, M. Tomana,, A. Kobata,, H. Ohbayashi,, T. Endo,, and C. Svanborg-Edén. 1990. Secretory immunoglobulin A carries oligosaccharide receptors for Escherichia coli type 1 fimbrial lectin. Infect. Immun. 58: 3073 3077.
148. Wu, X.,, T. T. Sun,, and J. J. Medina. 1996. In vitro binding of type 1-fimbriated Escherichia coli to uroplakins 1a and 1b: relation to urinary tract infections. Proc. Natl. Acad. Sci. USA 93: 9630 9635.
149. Wullt, B.,, G. Bergsren,, H. Fischer,, G. Godaly,, D. Karpman,, I. Leijonhufvud,, A. C. Lundstedt,, P. Samuelsson,, M. Samuelsson,, M. Svensson,, and C. Svanborg. 2003. The host response to urinary tract infection. Infect. Dis. Clin. North Am. 17: 279 301.
150. Wullt, B.,, G. Bergsten,, H. Connell,, P. Röllano,, N. Gebretsadik,, R. Hull,, and C. Svanborg. 2000. P fimbriae enhance the early establishment of Escherichia coli in the human urinary tract. Mol. Microbiol. 38: 456 464.
151. Wullt, B.,, G. Bergsten,, H. Connell,, P. Röllano,, N. Gebratsedik,, L. Hang,, and C. Svanborg. 2001. P-fimbriae trigger mucosal responses to Escherichia coli in the human urinary tract. Cell. Microbiol. 3: 255 264.
152. Yamamoto, S.,, T. Tsukamoto,, A. Terai,, H. Kurazono,, Y. Takeda,, and O. Yoshida. 1995. Distribution of virulence factors in Escherichia coli isolated from urine of cystitis patients. Microbiol. Immunol. 39: 401 404.
153. Zarember, K. A.,, and P. J. Godowski. 2002. Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNA in leukocytes in response to microbes, their products and cytokines. J. Immunol. 168: 554 561.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error