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

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


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
Urinary Tract Infections
Surface Receptors
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


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


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 82:57245727.
2. Abraham, S. N.,, and A. Michael. 1998. Mast cells and basophils in innate immunity. Semin. Immunol. 10:373381.
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. 167:16091616.
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. 61:602609.
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. 92:780785.
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. 59:29152921.
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 42:791798.
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. 3:153158.
9. Bäckhed, F.,, L. Meijer,, S. Normark,, and A. Richter-Dahlfors. 2002. TLR4-dependent recognition of lipopolysaccharide by epithelial cells requires sCD14. Cell. Microbiol. 4:493501.
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. 5:10571063.
11. Baggiolini, M.,, B. Dewald,, and B. Moser. 1994. Interleukin- 8 and related chemotactic cytokines—CXC and CC chemokines. Adv. Immunol. 55:97179.
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. 45:10791093.
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 389:636639.
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. 78:455460.
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. 189:17341742.
16. Blomfield, I.,, and M. van der Woude,. 2002. Regulation and function of phase variation in Escherichia coli, p. 89113. 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. 23:705717.
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. 175:2736.
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. 260:85458551.
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. 27:10031054.
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. 10:441449.
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 265:682684.
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. 31:329334.
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 93:98279832.
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. 57:33833388.
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. 185:18311840.
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 105:733743.
28. Donnenberg, M. S.,, and R. A. Welsh,. 1996. Virulence determinants of uropathogenic Escherichia coli, p. 135174. 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. 70:335348.
30. Esposito, D.,, and J. J. Scocca. 1997. The integrase family of tyrosine recombinases: evolution of a conserved active site domain. Nucleic Acids Res. 25:36053614.
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. 192:881890.
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. 40:3751.
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):S56S60.
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. 21:725738.
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. 263:53625367.
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. 30:725735.
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: 34513456.
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. 165:52875294.
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. 69:899906.
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. 8:213225.
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. 23:10891097.
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. 46:839844.
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. 31:564570.
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. 40:265272.
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. 162:30373044.
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. 182:17381748.
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. 159:21852192.
48. Hannun, Y. A. 1994. The sphingomyelin cycle and the second messenger function of ceramide. J. Biol. Chem. 269: 31253128.
49. Hanson, M. S.,, and C. C. Brinton, Jr. 1988. Identification and characterization of E. coli type 1 pilus tip adhesion protein. Nature 332:265268.
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. 180:12201229.
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 52:269279.
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. 59:421427.
53. Hedges, S.,, M. Svensson,, and C. Svanborg. 1992. Interleukin- 6 response of epithelial cell lines to bacterial stimulation in vitro. Infect. Immun. 60:12951301.
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. 39:542552.
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. 33:693703.
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. 183:10371044.
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. 29:12971306.
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. 195:559570.
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. 168:45314537.
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. 33:933938.
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 73:887901.
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. 12:837847.
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. 168:52335239.
64. Johnson, J. 1991. Virulence factors in Escherichia coli urinary tract infection. Clin. Microbiol Rev. 4:80128.
65. Jones, C. H.,, K. Dodson,, and S. Hultgren,. 1996. Structure, function, and assembly of adhesive P pili, p. 175219. 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:663666.
67. Kass, E. H. 1956. Asymptomatic infections in the urinary tract. Trans. Assoc. Am. Physicians 69:5664.
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. 4:231238.
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. 58:19951998.
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 356:252255.
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. 7:229237.
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. 270:90179025.
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. 8:127134.
76. Leffler, H.,, and C. Svanborg-Edén. 1981. Glycolipid receptors for Escherichia coli on human erythrocytes and uroepithelial cells. Infect. Immun. 34:920929.
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 86:973983.
78. Levin, B. R.,, and C. Svanborg. 1990. Selection and evolution of virulence in bacteria: an ecumenical excursion and modest suggestion. Parasitology 100(Suppl.):S103S115.
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 328:8487.
80. Lindberg, U. 1975. Asymptomatic bacteriuria in school girls. V. The clinical course and response to treatment. Acta Paediatr. Scand. 64:718724.
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. 59:10861092.
82. Lomberg, H.,, U. Jodal,, C. Svanborg Eden,, H. Leffler,, and B. Samuelsson. 1981. P1 blood group and urinary tract infection. Lancet i:551552.
83. Mabeck, C. E.,, F. Orskov,, and I. Orskov. 1971. Escherichia coli serotypes and renal involvement in urinary-tract infection. Lancet i:13121314.
84. Marcus, D. M.,, M. Naiki,, and S. K. Kundu. 1976. Abnormalities in the glycosphingolipid content of human Pk and p erythrocytes. Proc. Natl. Acad. Sci. USA 73:32633267.
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. 19:28032812.
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. 10:143155.
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: 45724579.
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. 164:59986004.
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. 3:667672.
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: 11521156.
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. 75:347360.
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. 164:558561.
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 93:125131.
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. 276:1022910233.
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. 116:95100.
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. 162:1723.
98. Orskov, I.,, C. Svanborg Edén,, and F. Orskov. 1988. Aerobactin production of serotyped Escherichia coli from urinary tract infections. Med. Microbiol. Immunol. 177:914.
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. 170:39773985.
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. 276:99249930.
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. 171:625631.
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: 518524.
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 282:20852088.
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. 31:17471757.
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. 189:615625.
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 95:588593.
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. 209:111116.
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. 72:31793186.
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 267:721729.
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. 259:336344.
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. 71:14701480.
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. 138:34753480.
114. Sharon, N.,, Y. Eshdat,, J. Silverblatt,, and I. Ofek. 1981. Bacterial adherence to cell surface sugars. Ciba Found. Symp. 80:119141.
115. Sharon, N. 1987. Bacterial lectins, cell-cell recognition and infectious disease. FEBS Lett. 217:145157.
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. 189:17771782.
117. Smiley, S. T.,, J. A. King,, and W. W. Hancoock. 2001. Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J. Immunol. 167:28872894.
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. 177:36803686.
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. 176:748755.
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. 97:359365.
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. 168:179185.
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. 13:7784.
123. Stamm, W. E.,, and S. R. Norrby. 2001. Urinary tract infections: disease panorama and challenges. J. Infect. Dis. 183(Suppl. 1):S1S4.
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. 156:870877.
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. 33:563570.
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. 223240. 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:490492.
128. Svanborg-Edén, C.,, B. Eriksson,, and L. A. Hanson. 1977. Adhesion of Escherichia coli to human uroepithelial cells in vitro. Infect. Immun. 18:767774.
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. 44:672680.
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 33:175188.
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 298:560562.
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. 55:12241232.
133. Svensson, M.,, B. Frendéus,, T. Butters,, F. Platt,, R. Dwek,, and C. Svanborg. 2003. Glycolipid depletion in antimicrobial therapy. Mol. Microbiol. 47:453461.
134. Takeda, K.,, T. Kaisho,, and S. Akira. 2003. Toll-like receptors. Annu. Rev. Immunol. 21:335376.
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. 195:99111.
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. 62:52965304.
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. 276:3133231339.
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. 277:1510715112.
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:13661369.
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. 43:149155.
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. 56:26152622.
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 98:1215612161.
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. 158:221223.
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. 152:315321.
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. 136143. 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. 56:25312537.
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. 58:30733077.
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 93:96309635.
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. 17:279301.
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. 38:456464.
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. 3:255264.
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. 39:401404.
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. 168:554561.

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