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Chapter 23 : How Noninvasive Pathogens Induce Disease: Lessons from Enteropathogenic and Enterohemorrhagic

Authors: Bruce A. Vallance1, Crystal Chan2, B. Brett Finlay3
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Affiliations: 1: Biotechnology Laboratory, University of British Columbia, Vancouver, B.C., V6T 1Z3, Canada; 2: Biotechnology Laboratory, University of British Columbia, Vancouver, B.C., V6T 1Z3, Canada; 3: Biotechnology Laboratory, University of British Columbia, Vancouver, B.C., V6T 1Z3, Canada
Content Type: Monograph
Publication Year: 2003

Category: Clinical Microbiology

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Abstract:

A novel focus of the work has been on defining the molecular and cellular mechanisms underlying the interactions between bacterial pathogens and host cells. During infection, enteropathogenic (EPEC) and enterohemorrhagic (EHEC) induce a characteristic ‘‘attaching and effacing’’ (A/E) histopathology on gut enterocytes. Since studies investigating the function of EPEC’s virulence factors are the most advanced, this chapter deals with EPEC as the prototype for the family of A/E-inducing pathogens. EPEC infection is estimated to cause the deaths of several hundred thousand children per year owing to dehydration and other complications. First widely recognized as the causative agent of hamburger disease, EHEC is a zoonotic pathogen that appears to be asymptomatically carried by various ruminants. Mutants lacking the bundle-forming pilus (BFP) plasmid still attach to host cells, but do not form microcolonies and produce fewer A/E lesions than wild-type EPEC. Immunofluorescence studies have shown that in addition to membrane-bound Tir, the tips of EPEC pedestals contain predominantly filamentous (F)-actin, as well as talin, α- actinin, ezrin, and several other cytoskeletal proteins. Diarrhea is undoubtedly the most prominent and widespread symptom associated with both EPEC and EHEC infection. Approaches using molecular biology, genetics, and cell biology have provided many new insights into how EPEC and related pathogens interact with and exploit host cells during the course of infection and how this ultimately leads to disease.

Citation: Vallance B, Chan C, Finlay B. 2003. How Noninvasive Pathogens Induce Disease: Lessons from Enteropathogenic and Enterohemorrhagic , p 423-438. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch23

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Type III Secretion System
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Tumor Necrosis Factor alpha
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Bacterial Proteins
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How Noninvasive Pathogens Induce Disease: Lessons from Enteropathogenic and Enterohemorrhagic Escherichia Coli
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Citation: Vallance B, Chan C, Finlay B. 2003. How Noninvasive Pathogens Induce Disease: Lessons from Enteropathogenic and Enterohemorrhagic , p 423-438. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch23
/content/10.1128/9781555817848.chap23.fig23-1
FIGURE 1

Transmission electron micrograph of A/E lesions in rabbit intestinal epithelial tissue (Peyer's patch) caused by the REPEC O103. Bacteria are labeled with “B”; pedestals are labeled with “P.” (×20,000.) (Photograph courtesy of Ursula Heczko, Biotechnology Laboratory, University of British Columbia, modified with permission from reference .)

10.1128/9781555817848/fig23-1_thmb.gif
10.1128/9781555817848/fig23-1.gif
Image of FIGURE 1
FIGURE 1

Transmission electron micrograph of A/E lesions in rabbit intestinal epithelial tissue (Peyer's patch) caused by the REPEC O103. Bacteria are labeled with “B”; pedestals are labeled with “P.” (×20,000.) (Photograph courtesy of Ursula Heczko, Biotechnology Laboratory, University of British Columbia, modified with permission from reference .)

Citation: Vallance B, Chan C, Finlay B. 2003. How Noninvasive Pathogens Induce Disease: Lessons from Enteropathogenic and Enterohemorrhagic , p 423-438. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch23
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FIGURE 2

The structure of the EPEC-induced pedestal. EPEC intimately attaches to the host cell through intimin-Tir binding. Several cytoskeletal proteins including α-actinin, talin, and Nck are recruited to the tip of the pedestal. Talin binds to Tir, but to which region is unknown; however, α-actinin binds to the N terminus of Tir, while Nck binds to the phosphotyrosine 474 at the C terminus of Tir. Binding of Nck is required for the recruitment of N-WASP and the Arp 2/3 complex, resulting in the nucleation of actin. F-actin, as well as many other host proteins, is found along the length of the pedestal while non-muscle myosin II and tropomyosin are found at the pedestal base. (Modified with permission from reference .)

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10.1128/9781555817848/fig23-2.gif
Image of FIGURE 2
FIGURE 2

The structure of the EPEC-induced pedestal. EPEC intimately attaches to the host cell through intimin-Tir binding. Several cytoskeletal proteins including α-actinin, talin, and Nck are recruited to the tip of the pedestal. Talin binds to Tir, but to which region is unknown; however, α-actinin binds to the N terminus of Tir, while Nck binds to the phosphotyrosine 474 at the C terminus of Tir. Binding of Nck is required for the recruitment of N-WASP and the Arp 2/3 complex, resulting in the nucleation of actin. F-actin, as well as many other host proteins, is found along the length of the pedestal while non-muscle myosin II and tropomyosin are found at the pedestal base. (Modified with permission from reference .)

Citation: Vallance B, Chan C, Finlay B. 2003. How Noninvasive Pathogens Induce Disease: Lessons from Enteropathogenic and Enterohemorrhagic , p 423-438. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch23
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FIGURE 3

Putative mechanisms underlying EPEC-induced diarrhea include increased epithelial permeability and alterations in Cl and HCO ion secretion. Contributing structural changes include loss of absorptive surfaces, while the translocated EPEC effector EspF has been implicated in the loss of tight junction integrity. Signaling events within infected cells may also play a role in diarrhea, including increased MAP kinase activity and IL-8 production, causing the recruitment of neutrophils resulting in tissue damage. (Modified with permission from reference .)

10.1128/9781555817848/fig23-3_thmb.gif
10.1128/9781555817848/fig23-3.gif
Image of FIGURE 3
FIGURE 3

Putative mechanisms underlying EPEC-induced diarrhea include increased epithelial permeability and alterations in Cl and HCO ion secretion. Contributing structural changes include loss of absorptive surfaces, while the translocated EPEC effector EspF has been implicated in the loss of tight junction integrity. Signaling events within infected cells may also play a role in diarrhea, including increased MAP kinase activity and IL-8 production, causing the recruitment of neutrophils resulting in tissue damage. (Modified with permission from reference .)

Citation: Vallance B, Chan C, Finlay B. 2003. How Noninvasive Pathogens Induce Disease: Lessons from Enteropathogenic and Enterohemorrhagic , p 423-438. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch23
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References

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1. Abe, A.,, U. Heczko,, R. G. Hegele,, and B. B. Finlay. 1998. Two enteropathogenic Escherichia coli type III secreted proteins, EspA and EspB, are virulence factors. J. Exp. Med. 188:1907–1916.
2. Cantarelli, V. V.,, A. Takahashi,, I. Yanagihara,, Y. Akeda,, K. Imura,, T. Kodoma,, G. Kono,, Y. Sato,, and T. Honda. 2001. Talin, a host cell protein, interacts directly with the translocated intimin receptor, Tir, of enteropathogenic Escherichia coli, and is essential for pedestal formation. Cell. Microbiol. 3:745–751.
3. Celli, J.,, M. Olivier,, and B. B. Finlay. 2001. Enteropathogenic Escherichia coli mediates antiphagocytosis through the inhibition of PI 3-kinase-dependent pathways. EMBO J. 20:1245–1258.
4. Cornelis, G. R.,, and F. Van Gijsegem. 2000. Assembly and function of type III secretory systems. Annu. Rev. Microbiol. 54:735–774.
5. Crane, J. K.,, B. P. McNamara,, and M. S. Donnenberg. 2001. Role of EspF in host cell death induced by enteropathogenic Escherichia coli. Cell. Microbiol. 2:197–211.
5a. Crane, J. K.,, and J. S. Oh. 1997. Activation of host cell protein kinase C by enteropathogenic Escherichia coli. Infect. Immun. 65:3277–3285.
6. Czerucka, D.,, S. Dahan,, B. Mograbi,, B. Rossi,, and P. Rampal. 2001. Implication of mitogen-activated protein kinases in T84 cell responses to enteropathogenic Escherichia coli infection. Infect. Immun. 69:1298–1305.
7. de Grado, M.,, C. M. Rosenberger,, A. Gauthier,, B. A. Vallance,, and B. B. Finlay. 2001. Enteropathogenic Escherichia coli infection induces expression of the early growth response factor by activating mitogen-activated protein kinase cascades in epithelial cells. Infect. Immun. 69:6217–6224.
8. Deng, W.,, Y. Li,, B. A. Vallance,, and B. B. Finlay. 2001. Locus of enterocyte effacement from Citrobacter rodentium: sequence analysis and evidence for horizontal transfer among attaching and effacing pathogens. Infect. Immun. 69:6323–6335.
9. DeVinney, R.,, J. L. Puente,, A. Gauthier,, D. Goosney,, and B. B. Finlay. 2001. Enterohaemorrhagic Escherichia coli use a different Tir-based mechanism for pedestal formation. Mol. Microbiol. 41:1445–1458.
10. DeVinney, R.,, M. Stein,, D. Reinscheid,, A. Abe,, S. Ruschkowski,, and B. B. Finlay. 1999. Enterohemorrhagic Escherichia coli O157: H7 produces Tir, which is translocated to the host cell membrane but is not tyrosine phosphorylated. Infect. Immun. 67:2389–2398.
11. Donnenberg, M. S.,, and T. S. Whittam. 2001. Pathogenesis and evolution of virulence in enteropathogenic and enterohemorrhagic Escherichia coli. J. Clin. Invest. 107:539–548.
12. Elliott, S. J.,, E. O. Krejany,, J. L. Mellies,, R. M. Robins-Browne,, C. Sasakawa,, and J. B. Kaper. 2001. EspG, a novel type III system-secreted protein from enteropathogenic Escherichia coli with similarities to VirA of Shigella flexneri. Infect. Immun. 69:4027–4033.
13. Frankel, G.,, A. D. Philipps,, L. R. Trabulsi,, S. Knutton,, G. Dougan,, and S. Matthews. 2001. Intimin and the host cell—is it bound to end in Tir(s)? Trends Microbiol. 9:214–218.
14. Ghaem-Maghami, M.,, C. P. Simmons,, S. Daniell,, M. Pizza,, D. Lewis,, G. Frankel,, and G. Dougan. 2001. Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium. Infect. Immun. 69:5597–5605.
15. Goncalves, N. S.,, M. Ghaem-Maghami,, G. Monteleone,, G. Frankel,, G. Dougan,, D. J. Lewis,, C. P. Simmons,, and T. T. MacDonald. 2001. Critical role for tumor necrosis factor alpha in controlling the number of lumenal pathogenic bacteria and immunopathology in infectious colitis. Infect. Immun. 69:6651–6659.
16. Goosney, D. L.,, R. DeVinney,, and B. B. Finlay. 2001. Recruitment of cytoskeletal and signaling proteins to enteropathogenic and enterohemorrhagic Escherichia coli pedestals. Infect. Immun. 69:3315–3322.
17. Goosney, D. L.,, R. DeVinney,, R. A. Pfuetzner,, E. A. Frey,, N. C. Strynadka,, and B. B. Finlay. 2000. Enteropathogenic E. coli translocated intimin receptor, Tir, interacts directly with alpha actinin. Curr. Biol. 10:735–738.
18. Gruenheid, S.,, R. DeVinney,, F. Bladt,, D. Goosney,, S. Gelkop,, G. D. Gish,, T. Pawson,, and B. B. Finlay. 2001. Enteropathogenic E. coli Tir binds Nck to initiate actin pedestal formation in host cells. Nat. Cell. Biol. 3:856–859.
19. Hecht, G. 2001. Microbes and microbial toxins: paradigms for microbial-mucosal interactions. VII. Enteropathogenic Escherichia coli: physiological alterations from an extracellular position. Am. J. Physiol. Gastrointest. Liver Physiol. 281:G1–G7.
20. Higgins, L. M.,, G. Frankel,, I. Connerton,, N. S. Goncalves,, G. Dougan,, and T. T. MacDonald. 1999. Role of bacterial intimin in colonic hyperplasia and inflammation. Science 285:588–591.
21. Kalman, D.,, O. D. Weiner,, D. L. Goosney,, J. W. Sedat,, B. B. Finlay,, A. Abe,, and J. M. Bishop. 1999. Enteropathogenic E. coli acts through WASP and Arp2/3 complex to form actin pedestals. Nat. Cell. Biol. 1:389–391.
22. Kenny, B. 2001. The enterohaemorrhagic Escherichia coli (serotype O157:H7) Tir molecule is not functionally interchangeable for its enteropathogenic E. coli (serotype O127:H6) homologue. Cell. Microbiol. 3:499–510.
23. Kenny, B.,, and J. Warawa. 2001. Enteropathogenic Escherichia coli (EPEC) Tir receptor molecule does not undergo full modification when introduced into host cells by EPECindependent mechanisms. Infect. Immun. 69: 1444–1453.
24. Kenny, B.,, and M. Jepson. 2000. Targeting of an enteropathogenic Escherichia coli (EPEC) effector protein to host mitochondria. Cell. Microbiol. 2:579–590.
25. Kenny, B.,, R. D. DeVinney,, M. Stein,, D. J. Reinscheid,, E. A. Frey,, and B. B. Finlay. 1997. Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell 91:511–520.
26. Klapproth, J. M.,, I. C. Scaletsky,, B. P. Mc-Namara,, L. C. Lai,, C. Malstrom,, S. P. James,, and M. S. Donnenberg. 2000. A large toxin from pathogenic Escherichia coli strains that inhibits lymphocyte activation. Infect. Immun. 68: 2148–2155.
27. Luo, Y.,, E. A. Frey,, R. A. Pfuetzner,, A. L. Creagh,, D. G. Knoechel,, C. A. Haynes,, B. B. Finlay,, and N. C. Strynadka. 2000. Crystal structure of enteropathogenic Escherichia coli intimin-receptor complex. Nature 405:1073–1077.
28. Luo, Y.,, M. G. Bertero,, E. A. Frey,, R. A. Pfuetzner,, M. R. Wenk,, L. Creagh,, S. L. Marcus,, D. Lim,, F. Sicheri,, C. Kay,, C. Haynes,, B. B. Finlay,, and N. C. Strynadka. 2001. Structural and biochemical characterization of the type III secretion chaperones CesT and SigE. Nat. Struct. Biol. 8:1031–1036.
29. Marches, O.,, J. P. Nougayrede,, S. Bouillier,, J. Mainil,, G. Charlier,, I. Raymond,, P. Pohl,, M. Boury,, J. De Rycke,, A. Milon,, and E. Oswald. 2000. Role of Tir and intimin in the virulence of rabbit enteropathogenic Escherichia coli serotype O103:H2. Infect. Immun. 68:2171–2182.
30. McNamara, B. P.,, A. Koutsouris,, C. B. O’Connell,, J. P. Nougayrede,, M. S. Donnenberg,, and G. Hecht. 2001. Translocated EspF protein from enteropathogenic Escherichia coli disrupts host intestinal barrier function. J. Clin. Invest. 107:621–629.
31. Nataro, J. P.,, and J. B. Kaper. 1998. Diarrheagenic Escherichia coli. Clin. Microbiol. Rev. 11: 142–201.
32. Newman, J. V.,, B. A. Zabel,, S. S. Jha,, and D. B. Schauer. 1999. Citrobacter rodentium espB is necessary for signal transduction and for infection of laboratory mice. Infect. Immun. 67:6019–6025.
33. Savkovic, S. D.,, A. Ramaswamy,, A. Koutsouris,, and G. Hecht. 2001. EPEC-activated ERK1/2 participate in inflammatory response but not tight junction barrier disruption. Am. J. Physiol. Gastrointest. Liver Physiol. 281:G890–G898.
34. Sekiya, K.,, M. Ohishi,, T. Ogino,, K. Tamano,, C. Sasakawa,, and A. Abe. 2001. Supermolecular structure of the enteropathogenic Escherichia coli type III secretion system and its direct interaction with the EspA-sheath-like structure. Proc. Natl. Acad. Sci. USA 98:11638–11643.
35. Simmons, C. P.,, S. Clare,, and G. Dougan. 2001. Understanding mucosal responsiveness: lessons from enteric bacterial pathogens. Semin. Immunol. 13:201–209.
36. Vallance, B. A.,, and B. B. Finlay. 2000. Exploitation of host cells by enteropathogenic Escherichia coli. Proc. Natl. Acad. Sci. USA 97:8799–8806.

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