1887

Chapter 27 : The Way Forward

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

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

The Way Forward, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818791/9781555818784_Chap27-1.gif /docserver/preview/fulltext/10.1128/9781555818791/9781555818784_Chap27-2.gif

Abstract:

We have observed a vertical leap into our understanding of EHEC’s virulence. In the past edition of this book, the locus of enterocyte effacement (LEE) and its encoded type 3 secretion system (T3SS) had been recently discovered ( ). However, few effectors were known at the time, with Tir ( ) and intimin ( ) dominating research on the molecular mechanisms involved in the formation of attaching and effacing (AE) lesions. Structural insights into T3SS came later, with the description of the EscF needle ( ) and the EspA filament ( ) forming the unique translocon of the EHEC and EPEC T3SSs. The number of effectors quickly expanded from the six LEE-encoded effectors, to the first hints that effectors encoded outside of the LEE existed ( ), to the large expansion of their repertoire ( ). Next-generation sequencing of many EHEC genomes also highlighted the fact that different strains of EHEC and enteropathogenic (EPEC) carry different combination of these effectors ( ). Vigorous research was initially devoted to understanding the mechanism through which EHEC engaged the actin cytoskeleton to form AE lesions. These studies involved Tir and intimin interactions, but also extensive studies in the EspFu/TccP effectors ( ). More recently, studies of non-AE-related effectors and their role in more discrete actin rearrangements, as well in modulation of the host immune response, have taken the front seat ( ). Looking forward, we need to understand how different combinations of T3SS effectors affect the virulence potential of EHEC strains. We are also starting to study the hierarchy of secretion of these effectors ( ) and how they work in concert. Knowledge of which effectors are acting within a mammalian cell at any given time, and how their functions amplify or antagonize their phenotypes, is the next frontier in understanding the role of these proteins in the bacterial/host interplay. Another still unresolved issue is how the T3SS is regulated to shift from secreting the translocon proteins (EspA, EspB, and EspD) to secreting effectors within epithelial cells. There is also the question of how the EspA filament is disassembled during the infection process to allow the close contact between the bacteria and the host. Finally, the big question that remains open is, how does EHEC cause diarrhea in the human intestine, and which are the main players in this disease process?

Citation: Sperandio V. 2015. The Way Forward, p 541-552. In Sperandio V, Hovde C (ed), Enterohemorrhagic and Other Shiga Toxin-Producing . ASM Press, Washington, DC. doi: 10.1128/9781555818791.ch27
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

References

/content/book/10.1128/9781555818791.chap27
1. McDaniel TK,, Jarvis KG,, Donnenberg MS,, Kaper JB . 1995. A genetic locus of enterocyte effacement conserved among diverse enterobacterial pathogens. Proc Natl Acad Sci USA 92 : 16641668.[PubMed] [CrossRef]
2. Jarvis KG,, Giron JA,, Jerse AE,, McDaniel TK,, Donnenberg MS,, Kaper JB . 1995. Enteropathogenic Escherichia coli contains a putative type III secretion system necessary for the export of proteins involved in attaching and effacing lesion formation. Proc Natl Acad Sci USA 92 : 79968000.[PubMed] [CrossRef]
3. Kenny B,, DeVinney R,, Stein M,, Reinscheid DJ,, Frey EA,, Finlay BB . 1997. Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell 91 : 511520.[PubMed] [CrossRef]
4. Jerse AE,, Yu J,, Tall BD,, Kaper JB . 1990. A genetic locus of enteropathogenic Escherichia coli necessary for the production of attaching and effacing lesions on tissue culture cells. Proc Natl Acad Sci USA 87 : 78397843.[PubMed] [CrossRef]
5. Sekiya K,, Ohishi M,, Ogino T,, Tamano K,, Sasakawa C,, Abe A . 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 : 1163811643.[PubMed] [CrossRef]
6. Knutton S,, Rosenshine I,, Pallen MJ,, Nisan I,, Neves BC,, Bain C,, Wolff C,, Dougan G,, Frankel G . 1998. A novel EspA-associated surface organelle of enteropathogenic Escherichia coli involved in protein translocation into epithelial cells. EMBO J 17 : 21662176.[PubMed] [CrossRef]
7. Deng W,, Puente JL,, Gruenheid S,, Li Y,, Vallance BA,, Vazquez A,, Barba J,, Ibarra JA,, O'Donnell P,, Metalnikov P,, Ashman K,, Lee S,, Goode D,, Pawson T,, Finlay BB . 2004. Dissecting virulence: systematic and functional analyses of a pathogenicity island. Proc Natl Acad Sci USA 101 : 35973602.[PubMed] [CrossRef]
8. Tobe T,, Beatson SA,, Taniguchi H,, Abe H,, Bailey CM,, Fivian A,, Younis R,, Matthews S,, Marches O,, Frankel G,, Hayashi T,, Pallen MJ . 2006. An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination. Proc Natl Acad Sci USA 103 : 1494114946.[PubMed] [CrossRef]
9. Hazen TH,, Sahl JW,, Fraser CM,, Donnenberg MS,, Scheutz F,, Rasko DA . 2013. Refining the pathovar paradigm via phylogenomics of the attaching and effacing Escherichia coli . Proc Natl Acad Sci USA 110 : 1281012815.[PubMed] [CrossRef]
10. de Grado M,, Abe A,, Gauthier A,, Steele-Mortimer O,, DeVinney R,, Finlay BB . 1999. Identification of the intimin-binding domain of Tir of enteropathogenic Escherichia coli . Cell Microbiol 1 : 717.[PubMed] [CrossRef]
11. DeVinney R,, Stein M,, Reinscheid D,, Abe A,, Ruschkowski S,, Finlay BB . 1999. Enterohemorrhagic Escherichia coli O157:H7 produces Tir, which is translocated to the host cell membrane but is not tyrosine phosphorylated. Infect Immun 67 : 23892398.[PubMed]
12. Luo Y,, Frey EA,, Pfuetzner RA,, Creagh AL,, Knoechel DG,, Haynes CA,, Finlay BB,, Strynadka NC . 2000. Crystal structure of enteropathogenic Escherichia coli intimin-receptor complex. Nature 405 : 10731077.[PubMed] [CrossRef]
13. Hartland EL,, Batchelor M,, Delahay RM,, Hale C,, Matthews S,, Dougan G,, Knutton S,, Connerton I,, Frankel G . 1999. Binding of intimin from enteropathogenic Escherichia coli to Tir and to host cells. Mol Microbiol 32 : 151158.[PubMed] [CrossRef]
14. Garmendia J,, Phillips AD,, Carlier MF,, Chong Y,, Schuller S,, Marches O,, Dahan S,, Oswald E,, Shaw RK,, Knutton S,, Frankel G . 2004. TccP is an enterohaemorrhagic Escherichia coli O157:H7 type III effector protein that couples Tir to the actin-cytoskeleton. Cell Microbiol 6 : 11671183.[PubMed] [CrossRef]
15. Liu H,, Magoun L,, Luperchio S,, Schauer DB,, Leong JM . 1999. The Tir-binding region of enterohaemorrhagic Escherichia coli intimin is sufficient to trigger actin condensation after bacterial-induced host cell signalling. Mol Microbiol 34 : 6781.[PubMed] [CrossRef]
16. Campellone KG,, Robbins D,, Leong JM . 2004. EspFU is a translocated EHEC effector that interacts with Tir and N-WASP and promotes Nck-independent actin assembly. Dev Cell 7 : 217228.[PubMed] [CrossRef]
17. Alto NM,, Scott JD . 2004. The role of A-Kinase anchoring proteins in cAMP-mediated signal transduction pathways. Cell Biochem Biophys 40 : 201208.[CrossRef]
18. Orchard RC,, Kittisopikul M,, Altschuler SJ,, Wu LF,, Suel GM,, Alto NM . 2012. Identification of F-actin as the dynamic hub in a microbial-induced GTPase polarity circuit. Cell 148 : 803815.[PubMed] [CrossRef]
19. Wong AR,, Clements A,, Raymond B,, Crepin VF,, Frankel G . 2012. The interplay between the Escherichia coli Rho guanine nucleotide exchange factor effectors and the mammalian RhoGEF inhibitor EspH. MBio 3 : e00250-11. doi:10.1128/mBio.00250-11. [CrossRef]
20. Hemrajani C,, Berger CN,, Robinson KS,, Marches O,, Mousnier A,, Frankel G . 2010. NleH effectors interact with Bax inhibitor-1 to block apoptosis during enteropathogenic Escherichia coli infection. Proc Natl Acad Sci USA 107 : 31293134.[PubMed] [CrossRef]
21. Pearson JS,, Riedmaier P,, Marches O,, Frankel G,, Hartland EL . 2011. A type III effector protease NleC from enteropathogenic Escherichia coli targets NF-kappaB for degradation. Mol Microbiol 80 : 219230.[PubMed] [CrossRef]
22. Hartland EL,, Leong JM . 2013. Enteropathogenic and enterohemorrhagic E. coli: ecology, pathogenesis, and evolution. Front Cell Infect Microbiol 3 : 15. [PubMed] [CrossRef]
23. Gao X,, Wang X,, Pham TH,, Feuerbacher LA,, Lubos ML,, Huang M,, Olsen R,, Mushegian A,, Slawson C,, Hardwidge PR . 2013. NleB, a bacterial effector with glycosyltransferase activity, targets GAPDH function to inhibit NF-kappaB activation. Cell Host Microbe 13 : 8799.[PubMed] [CrossRef]
24. Pham TH,, Gao X,, Tsai K,, Olsen R,, Wan F,, Hardwidge PR . 2012. Functional differences and interactions between the Escherichia coli type III secretion system effectors NleH1 and NleH2. Infect Immun 80 : 21332140.[PubMed] [CrossRef]
25. Berger CN,, Crepin VF,, Baruch K,, Mousnier A,, Rosenshine I,, Frankel G . 2012. EspZ of enteropathogenic and enterohemorrhagic Escherichia coli regulates type III secretion system protein translocation. MBio 3 : e00317-12. doi:10.1128/mBio.00317-12. [CrossRef]
26. Mills E,, Baruch K,, Aviv G,, Nitzan M,, Rosenshine I . 2013. Dynamics of the type III secretion system activity of enteropathogenic Escherichia coli . MBio 4 : e00303-13. doi:10.1128/mBio.00303-13. [CrossRef]
27. Farfan MJ,, Torres AG . 2012. Molecular mechanisms that mediate colonization of Shiga toxin-producing Escherichia coli strains. Infect Immun 80 : 903913.[PubMed] [CrossRef]
28. Obrig TG,, Karpman D . 2012. Shiga toxin pathogenesis: kidney complications and renal failure. Curr Top Microbiol Immunol 357 : 105136.[PubMed] [CrossRef]
29. Obata F,, Tohyama K,, Bonev AD,, Kolling GL,, Keepers TR,, Gross LK,, Nelson MT,, Sato S,, Obrig TG . 2008. Shiga toxin 2 affects the central nervous system through receptor globotriaosylceramide localized to neurons. J Infect Dis 198 : 13981406.[PubMed] [CrossRef]
30. Murray CS,, Tannock GW,, Simon MA,, Harmsen HJ,, Welling GW,, Custovic A,, Woodcock A . 2005. Fecal microbiota in sensitized wheezy and non-sensitized non-wheezy children: a nested case-control study. Clin Exp Allergy 35 : 741745.[PubMed] [CrossRef]
31. Tannock GW . 2005. New perceptions of the gut microbiota: implications for future research. Gastroenterol Clin North Am 34 : 361382, vii.[PubMed] [CrossRef]
32. Fukuda S,, Toh H,, Hase K,, Oshima K,, Nakanishi Y,, Yoshimura K,, Tobe T,, Clarke JM,, Topping DL,, Suzuki T,, Taylor TD,, Itoh K,, Kikuchi J,, Morita H,, Hattori M,, Ohno H . 2011. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469 : 543547.[PubMed] [CrossRef]
33. Sperandio V,, Torres AG,, Jarvis B,, Nataro JP,, Kaper JB . 2003. Bacteria-host communication: the language of hormones. Proc Natl Acad Sci USA 100 : 89518956.[PubMed] [CrossRef]
34. Pacheco AR,, Curtis MM,, Ritchie JM,, Munera D,, Waldor MK,, Moreira CG,, Sperandio V . 2012. Fucose sensing regulates bacterial intestinal colonization. Nature 492 : 113117.[PubMed] [CrossRef]
35. Njoroge JW,, Nguyen Y,, Curtis MM,, Moreira CG,, Sperandio V . 2012. Virulence meets metabolism: Cra and KdpE gene regulation in enterohemorrhagic Escherichia coli . MBio 3 : e00280-12. doi:10.1128/mBio.00280-12. [CrossRef]
36. Kendall MM,, Gruber CC,, Parker CT,, Sperandio V . 2012. Ethanolamine controls expression of genes encoding components involved in interkingdom signaling and virulence in enterohemorrhagic Escherichia coli O157:H7. MBio 3 : e00050-12. doi:10.1128/mBio.00050-12. [CrossRef]
37. de Sablet T,, Chassard C,, Bernalier-Donadille A,, Vareille M,, Gobert AP,, Martin C . 2009. Human microbiota-secreted factors inhibit shiga toxin synthesis by enterohemorrhagic Escherichia coli O157:H7. Infect Immun 77 : 783790.[PubMed] [CrossRef]
38. Gordon JI,, Klaenhammer TR . 2011. A rendezvous with our microbes. Proc Natl Acad Sci USA 108(Suppl 1): 45134515.[PubMed] [CrossRef]
39. Willing BP,, Vacharaksa A,, Croxen M,, Thanachayanont T,, Finlay BB . 2011. Altering host resistance to infections through microbial transplantation. PLoS One 6 : e26988. doi:10.1371/journal.pone.0026988 [PubMed] [CrossRef]
40. Kamada N,, Kim YG,, Sham HP,, Vallance BA,, Puente JL,, Martens EC,, Nunez G . 2012. Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science 336 : 13251329.[PubMed] [CrossRef]
41. Hughes DT,, Terekhova DA,, Liou L,, Hovde CJ,, Sahl JW,, Patankar AV,, Gonzalez JE,, Edrington TS,, Rasko DA,, Sperandio V . 2010. Chemical sensing in mammalian host-bacterial commensal associations. Proc Natl Acad Sci USA 107 : 98319836.[PubMed] [CrossRef]
42. Clarke MB,, Hughes DT,, Zhu C,, Boedeker EC,, Sperandio V . 2006. The QseC sensor kinase: a bacterial adrenergic receptor. Proc Natl Acad Sci USA 103 : 1042010425.[PubMed] [CrossRef]
43. Rasko DA,, Moreira CG,, Li DR,, Reading NC,, Ritchie JM,, Waldor MK,, Williams N,, Taussig R,, Wei S,, Roth M,, Hughes DT,, Huntley JF,, Fina MW,, Falck JR,, Sperandio V . 2008. Targeting QseC signaling and virulence for antibiotic development. Science 321 : 10781080.[PubMed] [CrossRef]
44. Hughes DT,, Clarke MB,, Yamamoto K,, Rasko DA,, Sperandio V . 2009. The QseC adrenergic signaling cascade in enterohemorrhagic E. coli (EHEC). PLoS Pathog 5 : e1000553. doi:10.1371/journal.ppat.1000553. [CrossRef]
45. Karmali MA,, Petric M,, Lim C,, Fleming PC,, Arbus GS,, Lior H . 1985. The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli . J Infect Dis 151 : 775782.[PubMed] [CrossRef]
46. Neely MN,, Friedman DI . 1998. Functional and genetic analysis of regulatory regions of coliphage H-19B: location of shiga-like toxin and lysis genes suggest a role for phage functions in toxin release. Mol Microbiol 28 : 12551267.[PubMed] [CrossRef]
47. Wagner PL,, Livny J,, Neely MN,, Acheson DW,, Friedman DI,, Waldor MK . 2002. Bacteriophage control of Shiga toxin 1 production and release by Escherichia coli . Mol Microbiol 44 : 957970.[PubMed] [CrossRef]
48. Slutsker L,, Ries AA,, Maloney K,, Wells JG,, Greene KD,, Griffin PM . 1998. A nationwide case-control study of Escherichia coli O157:H7 infection in the United States. J Infect Dis 177 : 962966.[PubMed] [CrossRef]
49. Wong CS,, Jelacic S,, Habeeb RL,, Watkins SL,, Tarr PI . 2000. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 342 : 19301936.[PubMed] [CrossRef]
50. Panos GZ,, Betsi GI,, Falagas ME . 2006. Systematic review: are antibiotics detrimental or beneficial for the treatment of patients with Escherichia coli O157:H7 infection? Aliment Pharmacol Ther 24 : 731742.[PubMed] [CrossRef]
51. Holtz LR,, Neill MA,, Tarr PI . 2009. Acute bloody diarrhea: a medical emergency for patients of all ages. Gastroenterology 136 : 18871898.[PubMed] [CrossRef]

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