1932

Abstract

In many parts of the world, enteropathogenic (EPEC) are a leading cause of death in children with diarrhea. Much of what we know about the pathogenesis of EPEC infections is based on the study of one or two prototypic strains that have provided deep insight into the precise mechanisms by which EPEC colonizes the intestine, evades host immunity, and spreads from person to person. In some cases, defining the biochemical activity of the host-interacting effector proteins from these prototypic strains has led to the discovery of novel post-translational protein modifications and new understandings of biology and host-pathogen interactions. However, genomic analysis of recent EPEC isolates has revealed that the EPEC pathotype is more diverse than previously appreciated. Although by definition all strains carry the locus of enterocyte effacement, the effector repertoires of different clonal groups are quite divergent, suggesting that there is still a great deal to learn about the genetic basis of EPEC virulence.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-120215-035138
2016-11-23
2024-06-22
Loading full text...

Full text loading...

/deliver/fulltext/genet/50/1/annurev-genet-120215-035138.html?itemId=/content/journals/10.1146/annurev-genet-120215-035138&mimeType=html&fmt=ahah

Literature Cited

  1. Alto NM, Shao F, Lazar CS, Brost RL, Chua G. 1.  et al. 2006. Identification of a bacterial type III effector family with G protein mimicry functions. Cell 124:133–45 [Google Scholar]
  2. Alto NM, Weflen AW, Rardin MJ, Yarar D, Lazar CS. 2.  et al. 2007. The type III effector EspF coordinates membrane trafficking by the spatiotemporal activation of two eukaryotic signaling pathways. J. Cell Biol. 178:1265–78 [Google Scholar]
  3. Arbeloa A, Bulgin RR, MacKenzie G, Shaw RK, Pallen MJ. 3.  et al. 2008. Subversion of actin dynamics by EspM effectors of attaching and effacing bacterial pathogens. Cell. Microbiol. 10:1429–41 [Google Scholar]
  4. Arbeloa A, Garnett J, Lillington J, Bulgin RR, Berger CN. 4.  et al. 2010. EspM2 is a RhoA guanine nucleotide exchange factor. Cell. Microbiol. 12:654–64 [Google Scholar]
  5. Arbeloa A, Oates CV, Marches O, Hartland EL, Frankel G. 5.  2011. Enteropathogenic and enterohemorrhagic Escherichia coli type III secretion effector EspV induces radical morphological changes in eukaryotic cells. Infect. Immun. 79:1067–76 [Google Scholar]
  6. Arthur JS, Ley SC. 6.  2013. Mitogen-activated protein kinases in innate immunity. Nat. Rev. Immunol. 13:679–92 [Google Scholar]
  7. Baruch K, Gur-Arie L, Nadler C, Koby S, Yerushalmi G. 7.  et al. 2011. Metalloprotease type III effectors that specifically cleave JNK and NF-κB. EMBO J. 30:221–31 [Google Scholar]
  8. Berger CN, Crepin VF, Baruch K, Mousnier A, Rosenshine I, Frankel G. 8.  2012. EspZ of enteropathogenic and enterohemorrhagic Escherichia coli regulates type III secretion system protein translocation. mBio 3:e00317–12 [Google Scholar]
  9. Berger CN, Crepin VF, Jepson MA, Arbeloa A, Frankel G. 9.  2009. The mechanisms used by enteropathogenic Escherichia coli to control filopodia dynamics. Cell. Microbiol. 11:309–22 [Google Scholar]
  10. Blasche S, Mortl M, Steuber H, Siszler G, Nisa S. 10.  et al. 2013. The E. coli effector protein NleF is a caspase inhibitor. PLOS ONE 8:e58937 [Google Scholar]
  11. Bray J. 11.  1945. Isolation of antigenically homogeneous strains of Bact. coli neopolitanum from summer diarrhoea of infants. J. Pathol. Bacteriol. 57:239–47 [Google Scholar]
  12. Bulgin R, Arbeloa A, Goulding D, Dougan G, Crepin VF. 12.  et al. 2009. The T3SS effector EspT defines a new category of invasive enteropathogenic E. coli (EPEC) which form intracellular actin pedestals. PLOS Pathog. 5:e1000683 [Google Scholar]
  13. Bulgin RR, Arbeloa A, Chung JC, Frankel G. 13.  2009. EspT triggers formation of lamellipodia and membrane ruffles through activation of Rac-1 and Cdc42. Cell. Microbiol. 11:217–29 [Google Scholar]
  14. Campellone KG, Rankin S, Pawson T, Kirschner MW, Tipper DJ, Leong JM. 14.  2004. Clustering of Nck by a 12-residue Tir phosphopeptide is sufficient to trigger localized actin assembly. J. Cell Biol. 164:407–16 [Google Scholar]
  15. Campellone KG, Robbins D, Leong JM. 15.  2004. EspFU is a translocated EHEC effector that interacts with Tir and N-WASP and promotes Nck-independent actin assembly. Dev. Cell 7:217–28 [Google Scholar]
  16. Caron E, Hall A. 16.  1998. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 282:1717–21 [Google Scholar]
  17. Celli J, Olivier M, Finlay BB. 17.  2001. Enteropathogenic Escherichia coli mediates antiphagocytosis through the inhibition of PI 3-kinase-dependent pathways. EMBO J. 20:1245–58 [Google Scholar]
  18. Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L. 18.  2000. Activation of the NF-κB pathway by caspase 8 and its homologs. Oncogene 19:4451–60 [Google Scholar]
  19. Clements A, Smollett K, Lee SF, Hartland EL, Lowe M, Frankel G. 19.  2011. EspG of enteropathogenic and enterohemorrhagic E. coli binds the Golgi matrix protein GM130 and disrupts the Golgi structure and function. Cell. Microbiol. 13:1429–39 [Google Scholar]
  20. Clements A, Stoneham CA, Furniss RC, Frankel G. 20.  2014. Enterohaemorrhagic Escherichia coli inhibits recycling endosome function and trafficking of surface receptors. Cell. Microbiol. 16:1693–705 [Google Scholar]
  21. Crepin VF, Girard F, Schuller S, Phillips AD, Mousnier A, Frankel G. 21.  2010. Dissecting the role of the Tir:Nck and Tir:IRTKS/IRSp53 signalling pathways in vivo. Mol. Microbiol. 75:308–23 [Google Scholar]
  22. Cui J, Yao Q, Li S, Ding X, Lu Q. 22.  et al. 2010. Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family. Science 329:1215–18 [Google Scholar]
  23. Daeron M, Jaeger S, Du Pasquier L, Vivier E. 23.  2008. Immunoreceptor tyrosine-based inhibition motifs: a quest in the past and future. Immunol. Rev. 224:11–43 [Google Scholar]
  24. Deng W, Puente JL, Gruenheid S, Li Y, Vallance BA. 24.  et al. 2004. Dissecting virulence: systematic and functional analyses of a pathogenicity island. PNAS 101:3597–602 [Google Scholar]
  25. Deng W, Yu HB, de Hoog CL, Stoynov N, Li Y. 25.  et al. 2012. Quantitative proteomic analysis of type III secretome of enteropathogenic Escherichia coli reveals an expanded effector repertoire for attaching/effacing bacterial pathogens. Mol. Cell. Proteom. 11:692–709 [Google Scholar]
  26. De Rycke J, Comtet E, Chalareng C, Boury M, Tasca C, Milon A. 26.  1997. Enteropathogenic Escherichia coli O103 from rabbit elicits actin stress fibers and focal adhesions in HeLa epithelial cells, cytopathic effects that are linked to an analog of the locus of enterocyte effacement. Infect. Immun. 65:2555–63 [Google Scholar]
  27. Dong N, Liu L, Shao F. 27.  2010. A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes macrophage phagocytosis. EMBO J. 29:1363–76 [Google Scholar]
  28. Dong N, Zhu Y, Lu Q, Hu L, Zheng Y, Shao F. 28.  2012. Structurally distinct bacterial TBC-like GAPs link Arf GTPase to Rab1 inactivation to counteract host defenses. Cell 150:1029–41 [Google Scholar]
  29. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L. 29.  et al. 2005. Diversity of the human intestinal microbial flora. Science 308:1635–38 [Google Scholar]
  30. Elliott SJ, Wainwright LA, McDaniel TK, Jarvis KG, Deng YK. 30.  et al. 1998. The complete sequence of the locus of enterocyte effacement (LEE) from enteropathogenic Escherichia coli E2348/69. Mol. Microbiol. 28:1–4 [Google Scholar]
  31. Gao X, Wan F, Mateo K, Callegari E, Wang D. 31.  et al. 2009. Bacterial effector binding to ribosomal protein s3 subverts NF-κB function. PLOS Pathog. 5:e1000708 [Google Scholar]
  32. Garmendia J, Phillips AD, Carlier MF, Chong Y, Schuller S. 32.  et al. 2004. TccP is an enterohaemorrhagic Escherichia coli O157:H7 type III effector protein that couples Tir to the actin-cytoskeleton. Cell. Microbiol. 6:1167–83 [Google Scholar]
  33. Giogha C, Lung TW, Muhlen S, Pearson JS, Hartland EL. 33.  2015. Substrate recognition by the zinc metalloprotease effector NleC from enteropathogenic Escherichia coli. Cell. Microbiol. 17:1766–78 [Google Scholar]
  34. Giogha C, Lung TW, Pearson JS, Hartland EL. 34.  2014. Inhibition of death receptor signaling by bacterial gut pathogens. Cytokine Growth Factor Rev. 25:235–43 [Google Scholar]
  35. Girao DM, Girao VB, Irino K, Gomes TA. 35.  2006. Classifying Escherichia coli. Emerg. Infect. Dis. 12:1297–99 [Google Scholar]
  36. Giron JA, Donnenberg MS, Martin WC, Jarvis KG, Kaper JB. 36.  1993. Distribution of the bundle-forming pilus structural gene (bfpA) among enteropathogenic Escherichia coli. J. Infect. Dis. 168:1037–41 [Google Scholar]
  37. Goosney DL, Celli J, Kenny B, Finlay BB. 37.  1999. Enteropathogenic Escherichia coli inhibits phagocytosis. Infect. Immun. 67:490–95 [Google Scholar]
  38. Green DR, Llambi F. 38.  2015. Cell death signaling. Cold Spring Harb. Perspect. Biol. 7:a006080 [Google Scholar]
  39. Grishin AM, Cherney M, Anderson DH, Phanse S, Babu M, Cygler M. 39.  2014. NleH defines a new family of bacterial effector kinases. Structure 22:250–59 [Google Scholar]
  40. Gruenheid S, DeVinney R, Bladt F, Goosney D, Gelkop S. 40.  et al. 2001. Enteropathogenic E. coli Tir binds Nck to initiate actin pedestal formation in host cells. Nat. Cell Biol. 3:856–59 [Google Scholar]
  41. Hartland EL, Batchelor M, Delahay RM, Hale C, Matthews S. 41.  et al. 1999. Binding of intimin from enteropathogenic Escherichia coli to Tir and to host cells. Mol. Microbiol. 32:151–58 [Google Scholar]
  42. Hazen TH, Donnenberg MS, Panchalingam S, Antonio M, Hossain A, Mandomando I. 42.  et al. 2016. Genomic diversity of EPEC associated with clinical presentations of differing severity. Nat. Microbiol. 1:15014 [Google Scholar]
  43. Hemrajani C, Berger CN, Robinson KS, Marches O, Mousnier A, Frankel G. 43.  2010. NleH effectors interact with Bax inhibitor-1 to block apoptosis during enteropathogenic Escherichia coli infection. PNAS 107:3129–34 [Google Scholar]
  44. Hsu Y, Jubelin G, Taieb F, Nougayrede JP, Oswald E, Stebbins CE. 44.  2008. Structure of the cyclomodulin Cif from pathogenic Escherichia coli. J. Mol. Biol. 384:465–77 [Google Scholar]
  45. Huang Z, Sutton SE, Wallenfang AJ, Orchard RC, Wu X. 45.  et al. 2009. Structural insights into host GTPase isoform selection by a family of bacterial GEF mimics. Nat. Struct. Mol. Biol. 16:853–60 [Google Scholar]
  46. Iizumi Y, Sagara H, Kabe Y, Azuma M, Kume K. 46.  et al. 2007. The enteropathogenic E. coli effector EspB facilitates microvillus effacing and antiphagocytosis by inhibiting myosin function. Cell Host Microbe 2:383–92 [Google Scholar]
  47. Imtiyaz HZ, Zhang Y, Zhang J. 47.  2005. Structural requirements for signal-induced target binding of FADD determined by functional reconstitution of FADD deficiency. J. Biol. Chem. 280:31360–67 [Google Scholar]
  48. Ingle DJT M, Edwards DJ, Hocking DM, Pickard DJ, Azzopardi KI. 48.  et al. 2016. Evolution of atypical enteropathogenic E. coli by repeated acquisition of LEE pathogenicity island variants. Nat. Microbiol. 1:15010 [Google Scholar]
  49. Jubelin G, Taieb F, Duda DM, Hsu Y, Samba-Louaka A. 49.  et al. 2010. Pathogenic bacteria target NEDD8-conjugated cullins to hijack host-cell signaling pathways. PLOS Pathog. 6:e1001128 [Google Scholar]
  50. Kalman D, Weiner OD, Goosney DL, Sedat JW, Finlay BB. 50.  et al. 1999. Enteropathogenic E. coli acts through WASP and Arp2/3 complex to form actin pedestals. Nat. Cell Biol. 1:389–91 [Google Scholar]
  51. Kanayama A, Seth RB, Sun L, Ea CK, Hong M. 51.  et al. 2004. TAB2 and TAB3 activate the NF-κB pathway through binding to polyubiquitin chains. Mol. Cell 15:535–48 [Google Scholar]
  52. Kaper JB, Nataro JP, Mobley HL. 52.  2004. Pathogenic Escherichia coli. Nat. Rev. Microbiol. 2:123–40 [Google Scholar]
  53. Keestra AM, Winter MG, Auburger JJ, Frassle SP, Xavier MN. 53.  et al. 2013. Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1. Nature 496:233–37 [Google Scholar]
  54. Kelly M, Hart E, Mundy R, Marches O, Wiles S. 54.  et al. 2006. Essential role of the type III secretion system effector NleB in colonization of mice by Citrobacter rodentium. Infect. Immun. 74:2328–37 [Google Scholar]
  55. Kenny B. 55.  1999. Phosphorylation of tyrosine 474 of the enteropathogenic Escherichia coli (EPEC) Tir receptor molecule is essential for actin nucleating activity and is preceded by additional host modifications. Mol. Microbiol. 31:1229–41 [Google Scholar]
  56. Kenny B, DeVinney R, Stein M, Reinscheid DJ, Frey EA, Finlay BB. 56.  1997. Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell 91:511–20 [Google Scholar]
  57. Kenny B, Ellis S, Leard AD, Warawa J, Mellor H, Jepson MA. 57.  2002. Co-ordinate regulation of distinct host cell signalling pathways by multifunctional enteropathogenic Escherichia coli effector molecules. Mol. Microbiol. 44:1095–107 [Google Scholar]
  58. Kenny B, Jepson M. 58.  2000. Targeting of an enteropathogenic Escherichia coli (EPEC) effector protein to host mitochondria. Cell. Microbiol 2:579–90 [Google Scholar]
  59. Kim DW, Lenzen G, Page AL, Legrain P, Sansonetti PJ, Parsot C. 59.  2005. The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes. PNAS 102:14046–51 [Google Scholar]
  60. Kim J, Thanabalasuriar A, Chaworth-Musters T, Fromme JC, Frey EA. 60.  et al. 2007. The bacterial virulence factor NleA inhibits cellular protein secretion by disrupting mammalian COPII function. Cell Host Microbe 2:160–71 [Google Scholar]
  61. Kim M, Ogawa M, Fujita Y, Yoshikawa Y, Nagai T. 61.  et al. 2009. Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment. Nature 459:578–82 [Google Scholar]
  62. Knodler LA, Crowley SM, Sham HP, Yang H, Wrande M. 62.  et al. 2014. Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens. Cell Host Microbe 16:249–56 [Google Scholar]
  63. Knutton S, Baldwin T, Williams PH, McNeish AS. 63.  1989. Actin accumulation at sites of bacterial adhesion to tissue culture cells: basis of a new diagnostic test for enteropathogenic and enterohemorrhagic Escherichia coli. Infect. Immun. 57:1290–98 [Google Scholar]
  64. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH. 64.  et al. 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382:209–22 [Google Scholar]
  65. Lamkanfi M, Dixit VM. 65.  2014. Mechanisms and functions of inflammasomes. Cell 157:1013–22 [Google Scholar]
  66. Lawrence JG, Ochman H. 66.  1998. Molecular archaeology of the Escherichia coli genome. PNAS 95:9413–17 [Google Scholar]
  67. Lee SF, Kelly M, McAlister A, Luck SN, Garcia EL. 67.  et al. 2008. A C-terminal class I PDZ binding motif of EspI/NleA modulates the virulence of attaching and effacing Escherichia coli and Citrobacter rodentium. Cell. Microbiol. 10:499–513 [Google Scholar]
  68. Levine MM, Edelman R. 68.  1984. Enteropathogenic Escherichia coli of classic serotypes associated with infant diarrhea: epidemiology and pathogenesis. Epidemiol. Rev. 6:31–51 [Google Scholar]
  69. Li S, Zhang L, Yao Q, Li L, Dong N. 69.  et al. 2013. Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains. Nature 501:242–46 [Google Scholar]
  70. Lin DY, Diao J, Zhou D, Chen J. 70.  2011. Biochemical and structural studies of a HECT-like ubiquitin ligase from Escherichia coli O157:H7. J. Biol. Chem. 286:441–49 [Google Scholar]
  71. Lozer DM, Souza TB, Monfardini MV, Vicentini F, Kitagawa SS. 71.  et al. 2013. Genotypic and phenotypic analysis of diarrheagenic Escherichia coli strains isolated from Brazilian children living in low socioeconomic level communities. BMC Infect. Dis. 13:418 [Google Scholar]
  72. Luo Y, Frey EA, Pfuetzner RA, Creagh AL, Knoechel DG. 72.  et al. 2000. Crystal structure of enteropathogenic Escherichia coli intimin-receptor complex. Nature 405:1073–77 [Google Scholar]
  73. Marches O, Batchelor M, Shaw RK, Patel A, Cummings N. 73.  et al. 2006. EspF of enteropathogenic Escherichia coli binds sorting nexin 9. J. Bacteriol. 188:3110–15 [Google Scholar]
  74. Marches O, Covarelli V, Dahan S, Cougoule C, Bhatta P. 74.  et al. 2008. EspJ of enteropathogenic and enterohaemorrhagic Escherichia coli inhibits opsono-phagocytosis. Cell. Microbiol. 10:1104–15 [Google Scholar]
  75. Marches O, Ledger TN, Boury M, Ohara M, Tu X. 75.  et al. 2003. Enteropathogenic and enterohaemorrhagic Escherichia coli deliver a novel effector called Cif, which blocks cell cycle G2/M transition. Mol. Microbiol. 50:1553–67 [Google Scholar]
  76. Martinez E, Schroeder GN, Berger CN, Lee SF, Robinson KS. 76.  et al. 2010. Binding to Na+/H+ exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH. Cell. Microbiol. 12:1718–31 [Google Scholar]
  77. McDaniel TK, Jarvis KG, Donnenberg MS, Kaper JB. 77.  1995. A genetic locus of enterocyte effacement conserved among diverse enterobacterial pathogens. PNAS 92:1664–68 [Google Scholar]
  78. Mills E, Baruch K, Aviv G, Nitzan M, Rosenshine I. 78.  2013. Dynamics of the type III secretion system activity of enteropathogenic Escherichia coli. mBio 4:e00303–13 [Google Scholar]
  79. Moon HW, Whipp SC, Argenzio RA, Levine MM, Giannella RA. 79.  1983. Attaching and effacing activities of rabbit and human enteropathogenic Escherichia coli in pig and rabbit intestines. Infect. Immun. 41:1340–51 [Google Scholar]
  80. Morikawa H, Kim M, Mimuro H, Punginelli C, Koyama T. 80.  et al. 2010. The bacterial effector Cif interferes with SCF ubiquitin ligase function by inhibiting deneddylation of Cullin1. Biochem. Biophys. Res. Commun. 401:268–74 [Google Scholar]
  81. Muhlen S, Ruchaud-Sparagano MH, Kenny B. 81.  2011. Proteasome-independent degradation of canonical NFκB complex components by the NleC protein of pathogenic Escherichia coli. J. Biol. Chem. 286:5100–7 [Google Scholar]
  82. Nadler C, Baruch K, Kobi S, Mills E, Haviv G. 82.  et al. 2010. The type III secretion effector NleE inhibits NF-κB Activation. PLOS Pathog. 6:e1000743 [Google Scholar]
  83. Nataro JP, Kaper JB. 83.  1998. Diarrheagenic Escherichia coli. Clin. Microbiol. Rev. 11:142–201 [Google Scholar]
  84. Newton HJ, Pearson JS, Badea L, Kelly M, Lucas M. 84.  et al. 2010. The type III effectors NleE and NleB from enteropathogenic E. coli and OspZ from Shigella block nuclear translocation of NF-κB p65. PLOS Pathog. 6:e1000898 [Google Scholar]
  85. Nougayrede JP, Boury M, Tasca C, Marches O, Milon A. 85.  et al. 2001. Type III secretion–dependent cell cycle block caused in HeLa cells by enteropathogenic Escherichia coli O103. Infect. Immun. 69:6785–95 [Google Scholar]
  86. Nougayrede JP, Foster GH, Donnenberg MS. 86.  2007. Enteropathogenic Escherichia coli effector EspF interacts with host protein Abcf2. Cell. Microbiol. 9:680–93 [Google Scholar]
  87. Pallett MA, Berger CN, Pearson JS, Hartland EL, Frankel G. 87.  2014. The type III secretion effector NleF of enteropathogenic Escherichia coli activates NF-κB early during infection. Infect. Immun. 82:4878–88 [Google Scholar]
  88. Papatheodorou P, Domanska G, Oxle M, Mathieu J, Selchow O. 88.  et al. 2006. The enteropathogenic Escherichia coli (EPEC) map effector is imported into the mitochondrial matrix by the TOM/Hsp70 system and alters organelle morphology. Cell. Microbiol. 8:677–89 [Google Scholar]
  89. Pearson JS, Giogha C, Ong SY, Kennedy CL, Kelly M. 89.  et al. 2013. A type III effector antagonizes death receptor signalling during bacterial gut infection. Nature 501:247–51 [Google Scholar]
  90. Pearson JS, Riedmaier P, Marches O, Frankel G, Hartland EL. 90.  2011. A type III effector protease NleC from enteropathogenic Escherichia coli targets NF-κB for degradation. Mol. Microbiol. 80:219–30 [Google Scholar]
  91. Petroski MD, Deshaies RJ. 91.  2005. Function and regulation of cullin-RING ubiquitin ligases. Nat. Rev. Mol. Cell Biol. 6:9–20 [Google Scholar]
  92. Pham TH, Gao X, Singh G, Hardwidge PR. 92.  2013. Escherichia coli virulence protein NleH1 interaction with the v-Crk sarcoma virus CT10 oncogene-like protein (CRKL) governs NleH1 inhibition of the ribosomal protein S3 (RPS3)/nuclear factor κB (NF-κB) pathway. J. Biol. Chem. 288:34567–74 [Google Scholar]
  93. Pham TH, Gao X, Tsai K, Olsen R, Wan F, Hardwidge PR. 93.  2012. Functional differences and interactions between the E. coli type III secretion system effectors NleH1 and NleH2. Infect. Immun. 80:2133–40 [Google Scholar]
  94. Piscatelli H, Kotkar SA, McBee ME, Muthupalani S, Schauer DB. 94.  et al. 2011. The EHEC type III effector NleL is an E3 ubiquitin ligase that modulates pedestal formation. PLOS ONE 6:e19331 [Google Scholar]
  95. Quitard S, Dean P, Maresca M, Kenny B. 95.  2006. The enteropathogenic Escherichia coli EspF effector molecule inhibits PI-3 kinase-mediated uptake independently of mitochondrial targeting. Cell. Microbiol. 8:972–81 [Google Scholar]
  96. Raymond B, Crepin VF, Collins JW, Frankel G. 96.  2011. The WxxxE effector EspT triggers expression of immune mediators in an Erk/JNK and NF-κB-dependent manner. Cell. Microbiol. 13:1881–93 [Google Scholar]
  97. Ridley AJ. 97.  2006. Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol. 16:522–29 [Google Scholar]
  98. Robins-Browne RM. 98.  1987. Traditional enteropathogenic Escherichia coli of infantile diarrhea. Rev. Infect. Dis. 9:28–53 [Google Scholar]
  99. Robinson KS, Mousnier A, Hemrajani C, Fairweather N, Berger CN, Frankel G. 99.  2010. The enteropathogenic Escherichia coli effector NleH inhibits apoptosis induced by Clostridiun difficile toxin B. Microbiology 156:1815–23 [Google Scholar]
  100. Roxas JL, Ryan K, Vedantam G, Viswanathan VK. 100.  2014. Enteropathogenic Escherichia coli dynamically regulates EGFR signaling in intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 307:G374–80 [Google Scholar]
  101. Roxas JL, Wilbur JS, Zhang X, Martinez G, Vedantam G, Viswanathan VK. 101.  2012. The enteropathogenic Escherichia coli-secreted protein EspZ inhibits host cell apoptosis. Infect. Immun. 80:3850–57 [Google Scholar]
  102. Royan SV, Jones RM, Koutsouris A, Roxas JL, Falzari K. 102.  et al. 2010. Enteropathogenic E. coli non-LEE encoded effectors NleH1 and NleH2 attenuate NF-κB activation. Mol. Microbiol. 78:1232–45 [Google Scholar]
  103. Ruchaud-Sparagano MH, Maresca M, Kenny B. 103.  2007. Enteropathogenic Escherichia coli (EPEC) inactivate innate immune responses prior to compromising epithelial barrier function. Cell. Microbiol. 9:1909–21 [Google Scholar]
  104. Ruchaud-Sparagano MH, Muhlen S, Dean P, Kenny B. 104.  2011. The enteropathogenic E. coli (EPEC) Tir effector inhibits NF-κB activity by targeting TNFα receptor-associated factors. PLOS Pathog. 7:e1002414 [Google Scholar]
  105. Schuller S, Lucas M, Kaper JB, Giron JA, Phillips AD. 105.  2009. The ex vivo response of human intestinal mucosa to enteropathogenic Escherichia coliinfection. Cell. Microbiol. 11:521–30 [Google Scholar]
  106. Sellin ME, Maslowski KM, Maloy KJ, Hardt WD. 106.  2015. Inflammasomes of the intestinal epithelium. Trends Immunol. 36:442–50 [Google Scholar]
  107. Selyunin AS, Reddick LE, Weigele BA, Alto NM. 107.  2014. Selective protection of an ARF1-GTP signaling axis by a bacterial scaffold induces bidirectional trafficking arrest. Cell Rep. 6:878–91 [Google Scholar]
  108. Selyunin AS, Sutton SE, Weigele BA, Reddick LE, Orchard RC. 108.  et al. 2011. The assembly of a GTPase-kinase signalling complex by a bacterial catalytic scaffold. Nature 469:107–11 [Google Scholar]
  109. Sham HP, Shames SR, Croxen MA, Ma C, Chan JM. 109.  et al. 2011. Attaching and effacing bacterial effector NleC suppresses epithelial inflammatory responses by inhibiting NF-κB and p38 mitogen-activated protein kinase activation. Infect. Immun. 79:3552–62 [Google Scholar]
  110. Shames SR, Bhavsar AP, Croxen MA, Law RJ, Mak SH. 110.  et al. 2011. The pathogenic Escherichia coli type III secreted protease NleC degrades the host acetyltransferase p300. Cell. Microbiol. 13:1542–57 [Google Scholar]
  111. Shames SR, Deng W, Guttman JA, de Hoog CL, Li Y. 111.  et al. 2010. The pathogenic E. coli type III effector EspZ interacts with host CD98 and facilitates host cell prosurvival signalling. Cell. Microbiol. 12:1322–39 [Google Scholar]
  112. Shames SR, Croxon MA, Deng W, Finlay BB. 112.  2011. The type III system-secreted effector EspZ localizes to host mitochondria and interacts with the translocase of inner mitochondrial membrane 17b. Infect. Immun. 79:4784–90 [Google Scholar]
  113. Sharma R, Tesfay S, Tomson FL, Kanteti RP, Viswanathan VK, Hecht G. 113.  2006. Balance of bacterial pro- and anti-inflammatory mediators dictates net effect of enteropathogenic Escherichia coli on intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 290:G685–94 [Google Scholar]
  114. Shaw RK, Smollett K, Cleary J, Garmendia J, Straatman-Iwanowska A. 114.  et al. 2005. Enteropathogenic Escherichia coli type III effectors EspG and EspG2 disrupt the microtubule network of intestinal epithelial cells. Infect. Immun. 73:4385–90 [Google Scholar]
  115. Shi J, Zhao Y, Wang Y, Gao W, Ding J. 115.  et al. 2014. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 514:187–92 [Google Scholar]
  116. Simovitch M, Sason H, Cohen S, Zahavi EE, Melamed-Book N. 116.  et al. 2010. EspM inhibits pedestal formation by enterohaemorrhagic Escherichia coli and enteropathogenic E. coli and disrupts the architecture of a polarized epithelial monolayer. Cell. Microbiol. 12:489–505 [Google Scholar]
  117. Smith K, Humphreys D, Hume PJ, Koronakis V. 117.  2010. Enteropathogenic Escherichia coli recruits the cellular inositol phosphatase SHIP2 to regulate actin-pedestal formation. Cell Host Microbe 7:13–24 [Google Scholar]
  118. Sohel I, Puente JL, Ramer SW, Bieber D, Wu CY, Schoolnik GK. 118.  1996. Enteropathogenic Escherichia coli: identification of a gene cluster coding for bundle-forming pilus morphogenesis. J. Bacteriol. 178:2613–28 [Google Scholar]
  119. Stone KD, Zhang HZ, Carlson LK, Donnenberg MS. 119.  1996. A cluster of fourteen genes from enteropathogenic Escherichia coli is sufficient for the biogenesis of a type IV pilus. Mol. Microbiol. 20:325–37 [Google Scholar]
  120. Thanabalasuriar A, Koutsouris A, Weflen A, Mimee M, Hecht G, Gruenheid S. 120.  2010. The bacterial virulence factor NleA is required for the disruption of intestinal tight junctions by enteropathogenic Escherichia coli. Cell. Microbiol. 12:31–41 [Google Scholar]
  121. Tomson FL, Viswanathan VK, Kanack KJ, Kanteti RP, Straub KV. 121.  et al. 2005. Enteropathogenic Escherichia coli EspG disrupts microtubules and in conjunction with Orf3 enhances perturbation of the tight junction barrier. Mol. Microbiol. 56:447–64 [Google Scholar]
  122. Toro TB, Toth JI, Petroski MD. 122.  2013. The cyclomodulin cycle inhibiting factor (CIF) alters cullin neddylation dynamics. J. Biol. Chem. 288:14716–26 [Google Scholar]
  123. Trabulsi LR, Keller R, Tardelli Gomes TA. 123.  2002. Typical and atypical enteropathogenic Escherichia coli. Emerg. Infect. Dis. 8:508–13 [Google Scholar]
  124. Tu X, Nisan I, Yona C, Hanski E, Rosenshine I. 124.  2003. EspH, a new cytoskeleton-modulating effector of enterohaemorrhagic and enteropathogenic Escherichia coli. Mol. Microbiol. 47:595–606 [Google Scholar]
  125. Turco MM, Sousa MC. 125.  2014. The structure and specificity of the type III secretion system effector NleC suggest a DNA mimicry mechanism of substrate recognition. Biochemistry 53:5131–39 [Google Scholar]
  126. Vlisidou I, Dziva F, La Ragione RM, Best A, Garmendia J. 126.  et al. 2006. Role of intimin-Tir interactions and the Tir-cytoskeleton coupling protein in the colonization of calves and lambs by Escherichia coli O157:H7. Infect. Immun. 74:758–64 [Google Scholar]
  127. Vlisidou I, Marches O, Dziva F, Mundy R, Frankel G, Stevens MP. 127.  2006. Identification and characterization of EspK, a type III secreted effector protein of enterohaemorrhagic Escherichia coli O157:H7. FEMS Microbiol. Lett. 263:32–40 [Google Scholar]
  128. Wan F, Weaver A, Gao X, Bern M, Hardwidge PR, Lenardo MJ. 128.  2011. IKKβ phosphorylation regulates RPS3 nuclear translocation and NF-κB function during infection with Escherichia coli strain O157:H7. Nat. Immunol. 12:335–43 [Google Scholar]
  129. Wang L, Yang JK, Kabaleeswaran V, Rice AJ, Cruz AC. 129.  et al. 2010. The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations. Nat. Struct. Mol. Biol. 17:1324–29 [Google Scholar]
  130. Weiss SM, Ladwein M, Schmidt D, Ehinger J, Lommel S. 130.  et al. 2009. IRSp53 links the enterohemorrhagic E. coli effectors Tir and EspFU for actin pedestal formation. Cell Host Microbe 5:244–58 [Google Scholar]
  131. Wickham ME, Brown NF, Boyle EC, Coombes BK, Finlay BB. 131.  2007. Virulence is positively selected by transmission success between mammalian hosts. Curr. Biol. 17:783–88 [Google Scholar]
  132. Wilbur JS, Byrd W, Ramamurthy S, Ledvina HE, Khirfan K. 132.  et al. 2015. The secreted effector protein EspZ is essential for virulence of rabbit enteropathogenic Escherichia coli. Infect. Immun. 83:1139–49 [Google Scholar]
  133. Wong AR, Clements A, Raymond B, Crepin VF, Frankel G. 133.  2012. The interplay between the Escherichia coli Rho guanine nucleotide exchange factor effectors and the mammalian RhoGEF inhibitor EspH. mBio 3:e00250–11 [Google Scholar]
  134. Wong AR, Pearson JS, Bright MD, Munera D, Robinson KS. 134.  et al. 2011. Enteropathogenic and enterohaemorrhagic Escherichia coli: even more subversive elements. Mol. Microbiol. 80:1420–38 [Google Scholar]
  135. Wong Fok Lung T, Giogha C, Creuzburg K, Ong SY, Pollock GL. 135.  et al. 2016. Mutagenesis and functional analysis of the bacterial arginine glycosyltransferase effector NleB1 from enteropathogenic Escherichia coli. Infect. Immun. 84:1346–60 [Google Scholar]
  136. Wong Fok Lung T, Pearson JS, Schuelein R, Hartland EL. 136.  2014. The cell death response to enteropathogenic Escherichia coli infection. Cell. Microbiol. 16:1736–45 [Google Scholar]
  137. Wu B, Skarina T, Yee A, Jobin MC, Dileo R. 137.  et al. 2010. NleG Type 3 effectors from enterohaemorrhagic Escherichia coli are U-Box E3 ubiquitin ligases. PLOS Pathog. 6:e1000960 [Google Scholar]
  138. Xu H, Yang J, Gao W, Li L, Li P. 138.  et al. 2014. Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome. Nature 513:237–41 [Google Scholar]
  139. Yan D, Quan H, Wang L, Liu F, Liu H. 139.  et al. 2013. Enteropathogenic Escherichia coli Tir recruits cellular SHP-2 through ITIM motifs to suppress host immune response. Cell Signal. 25:1887–94 [Google Scholar]
  140. Yan D, Wang X, Luo L, Cao X, Ge B. 140.  2012. Inhibition of TLR signaling by a bacterial protein containing immunoreceptor tyrosine-based inhibitory motifs. Nat. Immunol. 13:1063–71 [Google Scholar]
  141. Yao Q, Cui J, Zhu Y, Wang G, Hu L. 141.  et al. 2009. A bacterial type III effector family uses the papain-like hydrolytic activity to arrest the host cell cycle. PNAS 106:3716–21 [Google Scholar]
  142. Yao Q, Zhang L, Wan X, Chen J, Hu L. 142.  et al. 2014. Structure and specificity of the bacterial cysteine methyltransferase effector NleE suggests a novel substrate in human DNA repair pathway. PLOS Pathog. 10:e1004522 [Google Scholar]
  143. Yen H, Ooka T, Iguchi A, Hayashi T, Sugimoto N, Tobe T. 143.  2010. NleC, a type III secretion protease, compromises NF-κB activation by targeting p65/RelA. PLOS Pathog. 6:e1001231 [Google Scholar]
  144. Yen H, Sugimoto N, Tobe T. 144.  2015. Enteropathogenic Escherichia coli uses NleA to inhibit NLRP3 inflammasome activation. PLOS Pathog. 11:e1005121 [Google Scholar]
  145. Young JC, Clements A, Lang AE, Garnett JA, Munera D. 145.  et al. 2014. The Escherichia coli effector EspJ blocks Src kinase activity via amidation and ADP ribosylation. Nat. Commun. 5:5887 [Google Scholar]
  146. Zhang L, Ding X, Cui J, Xu H, Chen J. 146.  et al. 2012. Cysteine methylation disrupts ubiquitin-chain sensing in NF-κB activation. Nature 481:204–8 [Google Scholar]
/content/journals/10.1146/annurev-genet-120215-035138
Loading
/content/journals/10.1146/annurev-genet-120215-035138
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error