ENTRY hsa05130 Pathway NAME Pathogenic Escherichia coli infection - Homo sapiens (human) DESCRIPTION Enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are closely related pathogenic strains of Escherichia coli. The hallmark of EPEC/EHEC infections [DS:H00278 H00277] is induction of attaching and effacing (A/E) lesions that damage intestinal epithelial cells. The capacity to form A/E lesions is encoded mainly by the locus of enterocyte effacement (LEE) pathogenicity island. Tir, Map, EspF, EspG are known LEE-encoded effector proteins secreted via the type III secretion system, which is also LEE-encoded, into the host cell. EPEC and EHEC Tir's link the extracellular bacterium to the cell cytoskeleton. Map and EspF are involved in mitochondrion membrane permeabilization. EspG interacts with tubulins and stimulates microtubule destabilization. LEE-encoded adhesin or intimin (Eae) is exported via the general secretory pathway to the periplasm, where it is inserted into the outer membrane. In addition to Tir, two potential host cell-carried intimin receptors, beta1 integrin (ITGB1) and nucleolin (NCL), have so far been identified. The distinguishing feature of EHEC is the elaboration of Shiga-like toxin (Stx). Stx cleaves ribosomal RNA, thereby disrupting protein synthesis and killing the intoxicated epithelial or endothelial cells. CLASS Human Diseases; Infectious disease: bacterial PATHWAY_MAP hsa05130 Pathogenic Escherichia coli infection NETWORK ELEMENT N00926 Escherichia Tir to TLR2/4-MAPK signaling pathway N00927 Escherichia/Shigella NleE/OspZ to TNF-NFKB signaling pathway N00928 Escherichia NleB to TNF-NFKB signaling pathway N00929 Escherichia NleC to TNF-NFKB signaling pathway N00930 Escherichia NleD to TNF-JNK signaling pathway N00931 Escherichia NleD to TNF-p38 signaling pathway N00932 Escherichia NleH1 to TNF-NFKB signaling pathway N00933 Escherichia NleA to NLRP3 inflammasome signaling pathway N00935 Escherichia NleF to non-canonical inflammasome signaling pathway N00936 Escherichia NleB1 to crosstalk between extrinsic and intrinsic apoptotic pathways N00937 Escherichia NleF to extrinsic apoptotic pathway N00938 Escherichia NleH to intrinsic apoptotic pathway N00939 Escherichia EspF to intrinsic apoptotic pathway N01084 Escherichia EspG to ARNO-ARF-ACTB/G signaling pathway N01085 Escherichia EspG to ARNO-ARF-ACTB/G signaling pathway N01086 Escherichia EspT to RAC signaling pathway N01087 Escherichia EspW to RAC signaling pathway N01088 Escherichia EspH to LPA-GNA12/13-RhoA signaling pathway N01089 Escherichia EspM to LPA-GNA12/13-Rho signaling pathway N01091 Escherichia EspJ to IGG-FCGR-RAC signaling pathway N01092 Escherichia Eae/Tir to Actin signaling pathway N01093 Escherichia EspJ/Tir to Actin signaling pathway N01094 Escherichia Eae/Tir/TccP to Actin signaling pathway N01095 Escherichia Map to LPA-GNA12/13-RhoA signaling pathway N01096 Escherichia Map to CDC42 signaling pathway N01286 Escherichia EspG to Microtubule-RHOA signaling pathway N01288 Escherichia EspF to Tight junction-Actin signaling pathway N01290 Escherichia NleA to COPII vesicle formation N01292 Escherichia EspG to RAB1 signaling pathway N01294 Escherichia NleF to COPI vesicle formation DISEASE H00277 Enterohemorrhagic Escherichia coli (EHEC) infection H00278 Enteropathogenic Escherichia coli (EPEC) infection ORGANISM Homo sapiens (human) [GN:hsa] GENE 102723407 IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856] 6714 SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2] 2212 FCGR2A; Fc gamma receptor IIa [KO:K06472] 5879 RAC1; Rac family small GTPase 1 [KO:K04392] 9265 CYTH3; cytohesin 3 [KO:K18441] 27128 CYTH4; cytohesin 4 [KO:K18441] 9266 CYTH2; cytohesin 2 [KO:K18441] 9267 CYTH1; cytohesin 1 [KO:K18441] 382 ARF6; ADP ribosylation factor 6 [KO:K07941] 375 ARF1; ADP ribosylation factor 1 [KO:K07937] 10787 NCKAP1; NCK associated protein 1 [KO:K05750] 3071 NCKAP1L; NCK associated protein 1 like [KO:K05750] 23191 CYFIP1; cytoplasmic FMR1 interacting protein 1 [KO:K05749] 26999 CYFIP2; cytoplasmic FMR1 interacting protein 2 [KO:K05749] 10006 ABI1; abl interactor 1 [KO:K23649] 55845 BRK1; BRICK1 subunit of SCAR/WAVE actin nucleating complex [KO:K05752] 8936 WASF1; WASP family member 1 [KO:K05753] 10163 WASF2; WASP family member 2 [KO:K05748] 10810 WASF3; WASP family member 3 [KO:K06083] 10097 ACTR2; actin related protein 2 [KO:K17260] 57180 ACTR3B; actin related protein 3B [KO:K18584] 653857 ACTR3C; actin related protein 3C [KO:K18584] 10096 ACTR3; actin related protein 3 [KO:K18584] 10095 ARPC1B; actin related protein 2/3 complex subunit 1B [KO:K05757] 10552 ARPC1A; actin related protein 2/3 complex subunit 1A [KO:K05757] 10109 ARPC2; actin related protein 2/3 complex subunit 2 [KO:K05758] 10094 ARPC3; actin related protein 2/3 complex subunit 3 [KO:K05756] 10093 ARPC4; actin related protein 2/3 complex subunit 4 [KO:K05755] 10092 ARPC5; actin related protein 2/3 complex subunit 5 [KO:K05754] 81873 ARPC5L; actin related protein 2/3 complex subunit 5 like [KO:K05754] 71 ACTG1; actin gamma 1 [KO:K05692] 60 ACTB; actin beta [KO:K05692] 9138 ARHGEF1; Rho guanine nucleotide exchange factor 1 [KO:K12330] 387 RHOA; ras homolog family member A [KO:K04513] 998 CDC42; cell division cycle 42 [KO:K04393] 283446 MYO1H; myosin IH [KO:K10356] 4430 MYO1B; myosin IB [KO:K10356] 4542 MYO1F; myosin IF [KO:K10356] 4640 MYO1A; myosin IA [KO:K10356] 4641 MYO1C; myosin IC [KO:K10356] 4642 MYO1D; myosin ID [KO:K10356] 4643 MYO1E; myosin IE [KO:K10356] 64005 MYO1G; myosin IG [KO:K10356] 4644 MYO5A; myosin VA [KO:K10357] 4645 MYO5B; myosin VB [KO:K10357] 55930 MYO5C; myosin VC [KO:K10357] 4646 MYO6; myosin VI [KO:K10358] 4651 MYO10; myosin X [KO:K12559] 4627 MYH9; myosin heavy chain 9 [KO:K10352] 4628 MYH10; myosin heavy chain 10 [KO:K10352] 4629 MYH11; myosin heavy chain 11 [KO:K10352] 79784 MYH14; myosin heavy chain 14 [KO:K10352] 8976 WASL; WASP like actin nucleation promoting factor [KO:K23612] 9368 NHERF1; NHERF family PDZ scaffold protein 1 [KO:K13365] 7430 EZR; ezrin [KO:K08007] 2147 F2; coagulation factor II, thrombin [KO:K01313] [EC:3.4.21.5] 1902 LPAR1; lysophosphatidic acid receptor 1 [KO:K04289] 9170 LPAR2; lysophosphatidic acid receptor 2 [KO:K04291] 2846 LPAR4; lysophosphatidic acid receptor 4 [KO:K04275] 57121 LPAR5; lysophosphatidic acid receptor 5 [KO:K08390] 2149 F2R; coagulation factor II thrombin receptor [KO:K03914] 2768 GNA12; G protein subunit alpha 12 [KO:K04346] 10672 GNA13; G protein subunit alpha 13 [KO:K04639] 9826 ARHGEF11; Rho guanine nucleotide exchange factor 11 [KO:K12331] 23365 ARHGEF12; Rho guanine nucleotide exchange factor 12 [KO:K07532] 10376 TUBA1B; tubulin alpha 1b [KO:K07374] 7277 TUBA4A; tubulin alpha 4a [KO:K07374] 7278 TUBA3C; tubulin alpha 3c [KO:K07374] 7846 TUBA1A; tubulin alpha 1a [KO:K07374] 84790 TUBA1C; tubulin alpha 1c [KO:K07374] 51807 TUBA8; tubulin alpha 8 [KO:K07374] 112714 TUBA3E; tubulin alpha 3e [KO:K07374] 113457 TUBA3D; tubulin alpha 3d [KO:K07374] 79861 TUBAL3; tubulin alpha like 3 [KO:K07374] 84617 TUBB6; tubulin beta 6 class V [KO:K07375] 203068 TUBB; tubulin beta class I [KO:K07375] 81027 TUBB1; tubulin beta 1 class VI [KO:K07375] 7280 TUBB2A; tubulin beta 2A class IIa [KO:K07375] 10381 TUBB3; tubulin beta 3 class III [KO:K07375] 10382 TUBB4A; tubulin beta 4A class IVa [KO:K07375] 347688 TUBB8; tubulin beta 8 class VIII [KO:K07375] 347733 TUBB2B; tubulin beta 2B class IIb [KO:K07375] 10383 TUBB4B; tubulin beta 4B class IVb [KO:K07375] 9181 ARHGEF2; Rho/Rac guanine nucleotide exchange factor 2 [KO:K12791] 6093 ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1] 9475 ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1] 2534 FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2] 25 ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2] 55971 BAIAP2L1; BAR/IMD domain containing adaptor protein 2 like 1 [KO:K20127] 10458 BAIAP2; BAR/IMD domain containing adaptor protein 2 [KO:K05627] 4690 NCK1; NCK adaptor protein 1 [KO:K07365] 8440 NCK2; NCK adaptor protein 2 [KO:K19862] 147179 WIPF2; WAS/WASL interacting protein family member 2 [KO:K19475] 7456 WIPF1; WAS/WASL interacting protein family member 1 [KO:K19475] 644150 WIPF3; WAS/WASL interacting protein family member 3 [KO:K19475] 2017 CTTN; cortactin [KO:K06106] 3059 HCLS1; hematopoietic cell-specific Lyn substrate 1 [KO:K06106] 4691 NCL; nucleolin [KO:K11294] 3688 ITGB1; integrin subunit beta 1 [KO:K05719] 3553 IL1B; interleukin 1 beta [KO:K04519] 3554 IL1R1; interleukin 1 receptor type 1 [KO:K04386] 7099 TLR4; toll like receptor 4 [KO:K10160] 114609 TIRAP; TIR domain containing adaptor protein [KO:K05403] 4615 MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729] 7100 TLR5; toll like receptor 5 [KO:K10168] 3654 IRAK1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:2.7.11.1] 51135 IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1] 5777 PTPN6; protein tyrosine phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48] 5781 PTPN11; protein tyrosine phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48] 7189 TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27] 7124 TNF; tumor necrosis factor [KO:K03156] 7132 TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158] 8717 TRADD; TNFRSF1A associated via death domain [KO:K03171] 2597 GAPDH; glyceraldehyde-3-phosphate dehydrogenase [KO:K00134] [EC:1.2.1.12] 7186 TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27] 8737 RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1] 6885 MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25] 10454 TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403] 23118 TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404] 257397 TAB3; TGF-beta activated kinase 1 (MAP3K7) binding protein 3 [KO:K12793] 8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210] 1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467] [EC:2.7.11.10] 3551 IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10] 4792 NFKBIA; NFKB inhibitor alpha [KO:K04734] 4793 NFKBIB; NFKB inhibitor beta [KO:K02581] 4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580] 5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735] 6188 RPS3; ribosomal protein S3 [KO:K02985] 5594 MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24] 5595 MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24] 5599 MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24] 5602 MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24] 5601 MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24] 5600 MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24] 6300 MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24] 5603 MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24] 1432 MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24] 2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379] 3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448] 3569 IL6; interleukin 6 [KO:K05405] 3576 CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030] 8743 TNFSF10; TNF superfamily member 10 [KO:K04721] 8797 TNFRSF10A; TNF receptor superfamily member 10a [KO:K04722] 8795 TNFRSF10B; TNF receptor superfamily member 10b [KO:K04722] 356 FASLG; Fas ligand [KO:K04389] 355 FAS; Fas cell surface death receptor [KO:K04390] 8772 FADD; Fas associated via death domain [KO:K02373] 841 CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61] 7009 TMBIM6; transmembrane BAX inhibitor motif containing 6 [KO:K21889] 578 BAK1; BCL2 antagonist/killer 1 [KO:K14021] 581 BAX; BCL2 associated X, apoptosis regulator [KO:K02159] 54205 CYCS; cytochrome c, somatic [KO:K08738] 842 CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62] 836 CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56] 840 CASP7; caspase 7 [KO:K04397] [EC:3.4.22.60] 10061 ABCF2; ATP binding cassette subfamily F member 2 [KO:K06185] 4671 NAIP; NLR family apoptosis inhibitory protein [KO:K12807] 147945 NLRP4; NLR family pyrin domain containing 4 [KO:K22265] 114548 NLRP3; NLR family pyrin domain containing 3 [KO:K12800] 29108 PYCARD; PYD and CARD domain containing [KO:K12799] 834 CASP1; caspase 1 [KO:K01370] [EC:3.4.22.36] 837 CASP4; caspase 4 [KO:K04394] [EC:3.4.22.57 3.4.22.64] 3606 IL18; interleukin 18 [KO:K05482] 5058 PAK1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1] 5062 PAK2; p21 (RAC1) activated kinase 2 [KO:K04410] [EC:2.7.11.1] 5063 PAK3; p21 (RAC1) activated kinase 3 [KO:K05733] [EC:2.7.11.1] 5861 RAB1A; RAB1A, member RAS oncogene family [KO:K07874] 10427 SEC24B; SEC24 homolog B, COPII coat complex component [KO:K14007] 10802 SEC24A; SEC24 homolog A, COPII coat complex component [KO:K14007] 9632 SEC24C; SEC24 homolog C, COPII coat complex component [KO:K14007] 9871 SEC24D; SEC24 homolog D, COPII coat complex component [KO:K14007] 10972 TMED10; transmembrane p24 trafficking protein 10 [KO:K20352] 100506658 OCLN; occludin [KO:K06088] 1364 CLDN4; claudin 4 [KO:K06087] 1365 CLDN3; claudin 3 [KO:K06087] 1366 CLDN7; claudin 7 [KO:K06087] 149461 CLDN19; claudin 19 [KO:K06087] 10686 CLDN16; claudin 16 [KO:K06087] 23562 CLDN14; claudin 14 [KO:K06087] 24146 CLDN15; claudin 15 [KO:K06087] 26285 CLDN17; claudin 17 [KO:K06087] 49861 CLDN20; claudin 20 [KO:K06087] 5010 CLDN11; claudin 11 [KO:K06087] 51208 CLDN18; claudin 18 [KO:K06087] 53842 CLDN22; claudin 22 [KO:K06087] 7122 CLDN5; claudin 5 [KO:K06087] 9071 CLDN10; claudin 10 [KO:K06087] 9073 CLDN8; claudin 8 [KO:K06087] 9074 CLDN6; claudin 6 [KO:K06087] 9075 CLDN2; claudin 2 [KO:K06087] 9076 CLDN1; claudin 1 [KO:K06087] 9080 CLDN9; claudin 9 [KO:K06087] 137075 CLDN23; claudin 23 [KO:K06087] 100288814 CLDN34; claudin 34 [KO:K06087] 644672 CLDN25; claudin 25 [KO:K06087] 100132463 CLDN24; claudin 24 [KO:K06087] 9069 CLDN12; claudin 12 [KO:K06087] 7082 TJP1; tight junction protein 1 [KO:K05701] COMPOUND C00338 Lipopolysaccharide C00350 Phosphatidylethanolamine C00681 1-Acyl-sn-glycerol 3-phosphate REFERENCE PMID:29477730 AUTHORS Pinaud L, Sansonetti PJ, Phalipon A TITLE Host Cell Targeting by Enteropathogenic Bacteria T3SS Effectors. JOURNAL Trends Microbiol 26:266-283 (2018) DOI:10.1016/j.tim.2018.01.010 REFERENCE PMID:25588886 AUTHORS Santos AS, Finlay BB TITLE Bringing down the host: enteropathogenic and enterohaemorrhagic Escherichia coli effector-mediated subversion of host innate immune pathways. JOURNAL Cell Microbiol 17:318-32 (2015) DOI:10.1111/cmi.12412 REFERENCE PMID:26104206 AUTHORS Pearson JS, Hartland EL TITLE The Inflammatory Response during Enterohemorrhagic Escherichia coli Infection. JOURNAL Microbiol Spectr 2:EHEC-0012-2013 (2014) DOI:10.1128/microbiolspec.EHEC-0012-2013 REFERENCE PMID:21488979 AUTHORS Wong AR, Pearson JS, Bright MD, Munera D, Robinson KS, Lee SF, Frankel G, Hartland EL TITLE Enteropathogenic and enterohaemorrhagic Escherichia coli: even more subversive elements. JOURNAL Mol Microbiol 80:1420-38 (2011) DOI:10.1111/j.1365-2958.2011.07661.x REFERENCE PMID:23927593 AUTHORS Lai Y, Rosenshine I, Leong JM, Frankel G TITLE Intimate host attachment: enteropathogenic and enterohaemorrhagic Escherichia coli. JOURNAL Cell Microbiol 15:1796-808 (2013) DOI:10.1111/cmi.12179 REFERENCE PMID:27606286 AUTHORS Ugalde-Silva P, Gonzalez-Lugo O, Navarro-Garcia F TITLE Tight Junction Disruption Induced by Type 3 Secretion System Effectors Injected by Enteropathogenic and Enterohemorrhagic Escherichia coli. JOURNAL Front Cell Infect Microbiol 6:87 (2016) DOI:10.3389/fcimb.2016.00087 REFERENCE PMID:27617233 AUTHORS Yen H, Karino M, Tobe T TITLE Modulation of the Inflammasome Signaling Pathway by Enteropathogenic and Enterohemorrhagic Escherichia coli. JOURNAL Front Cell Infect Microbiol 6:89 (2016) DOI:10.3389/fcimb.2016.00089 REFERENCE PMID:27732847 AUTHORS Humphreys D, Singh V, Koronakis V TITLE Inhibition of WAVE Regulatory Complex Activation by a Bacterial Virulence Effector Counteracts Pathogen Phagocytosis. JOURNAL Cell Rep 17:697-707 (2016) DOI:10.1016/j.celrep.2016.09.039 REFERENCE PMID:20300064 AUTHORS Dong N, Liu L, Shao F TITLE A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes macrophage phagocytosis. JOURNAL EMBO J 29:1363-76 (2010) DOI:10.1038/emboj.2010.33 REFERENCE PMID:15318166 AUTHORS Matsuzawa T, Kuwae A, Yoshida S, Sasakawa C, Abe A. TITLE Enteropathogenic Escherichia coli activates the RhoA signaling pathway via the stimulation of GEF-H1. JOURNAL EMBO J 23:3570-82 (2004) DOI:10.1038/sj.emboj.7600359 REL_PATHWAY hsa04064 NF-kappa B signaling pathway hsa04210 Apoptosis hsa04530 Tight junction hsa04620 Toll-like receptor signaling pathway hsa04621 NOD-like receptor signaling pathway hsa04666 Fc gamma R-mediated phagocytosis hsa04810 Regulation of actin cytoskeleton KO_PATHWAY ko05130 ///