KEGG   PATHWAY: ko05131Help
Entry
ko05131                     Pathway                                

Name
Shigellosis
Description
Shigellosis, or bacillary dysentery, is an intestinal infection caused by Shigella, a genus of enterobacteria. Shigella are potential food-borne pathogens that are capable of colonizing the intestinal epithelium by exploiting epithelial-cell functions and circumventing the host innate immune response. During basolateral entry into the host-cell cytoplasm, Shigella deliver a subset of effectors into the host cells through the type III secretion system. The effectors induce membrane ruffling through the stimulation of the Rac1-WAVE-Arp2/3 pathway, enabling bacterial entry into the epithelial cells. During multiplication within the cells, Shigella secrete another subset of effectors. VirG induces actin polymerization at one pole of the bacteria, allowing the bacteria to spread intracellularly and to infect adjacent cells. OspF, OspG and IpaH(9.8) downregulate the production of proinflammatory cytokines such as IL-8, helping bacteria circumvent the innate immune response.
Class
09160 Human Diseases; 09167 Infectious diseases
BRITE hierarchy
Pathway map
ko05131  Shigellosis
ko05131

Ortholog table
Module
M00363  EHEC pathogenicity signature, Shiga toxin [PATH:ko05131]
Disease
H00299  Shigellosis
Orthology
K13287  invasin D
K13286  invasin C
K13285  invasin B
K06484  integrin alpha 5
K05719  integrin beta 1
K06256  CD44 antigen
K13742  protein IpgB1
K07863  Ras homolog gene family, member G
K12366  engulfment and cell motility protein 1
K18985  engulfment and cell motility protein 2
K19241  engulfment and cell motility protein 3
K13708  dedicator of cytokinesis protein 1
K04392  Ras-related C3 botulinum toxin substrate 1
K05753  WAS protein family, member 1
K05748  WAS protein family, member 2
K05754  actin related protein 2/3 complex, subunit 5
K05755  actin related protein 2/3 complex, subunit 4
K05756  actin related protein 2/3 complex, subunit 3
K05757  actin related protein 2/3 complex, subunit 1A/1B
K05758  actin related protein 2/3 complex, subunit 2
K05704  tyrosine-protein kinase Src [EC:2.7.10.2]
K06106  cortactin
K06619  abelson tyrosine-protein kinase 1 [EC:2.7.10.2]
K04438  proto-oncogene C-crk
K04393  cell division control protein 42
K12785  LEE-encoded effector EspG
K13284  invasin A
K05700  vinculin
K13085  phosphatidylinositol-4,5-bisphosphate 4-phosphatase [EC:3.1.3.78]
K13743  protein IpgB2
K05740  diaphanous 1
K04514  Rho-associated protein kinase 1 [EC:2.7.11.1]
K17388  Rho-associated protein kinase 2 [EC:2.7.11.1]
K12679  outer membrane protein IcsA
K13790  virulence protein IcsB
K05747  Wiskott-Aldrich syndrome protein
K05692  actin beta/gamma 1
K05759  profilin
K08339  autophagy-related protein 5
K08727  nucleotide-binding oligomerization domain-containing protein 1
K10165  nucleotide-binding oligomerization domain-containing protein 2
K08846  receptor-interacting serine/threonine-protein kinase 2 [EC:2.7.11.1]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04441  p38 MAP kinase [EC:2.7.11.24]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K02581  NF-kappa-B inhibitor beta
K04734  NF-kappa-B inhibitor alpha
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K10030  interleukin 8
K13450  phosphothreonine lyase [EC:4.2.3.-]
K13791  invasion plasmid antigen
K12836  splicing factor U2AF 35 kDa subunit
K13792  secreted effector OspG
K03362  F-box and WD-40 domain protein 1/11
K13728  mitotic spindle assembly checkpoint protein MAD2B
K13793  secreted effector OspE
K11006  shiga toxin subunit A
K11007  shiga toxin subunit B
K11011  enterotoxin Set1A
K11012  enterotoxin Set1B
Compound
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C04737  alpha-D-Galactosyl-(1->4)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide
Reference
  Authors
Schroeder GN, Hilbi H
  Title
Molecular pathogenesis of Shigella spp.: controlling host cell signaling, invasion, and death by type III secretion.
  Journal
Clin Microbiol Rev 21:134-56 (2008)
DOI:10.1128/CMR.00032-07
Reference
  Authors
Ogawa M, Handa Y, Ashida H, Suzuki M, Sasakawa C
  Title
The versatility of Shigella effectors.
  Journal
Nat Rev Microbiol 6:11-6 (2008)
DOI:10.1038/nrmicro1814
Reference
PMID:7591128
  Authors
Nataro JP, Seriwatana J, Fasano A, Maneval DR, Guers LD, Noriega F, Dubovsky F, Levine MM, Morris JG Jr
  Title
Identification and cloning of a novel plasmid-encoded enterotoxin of enteroinvasive Escherichia coli and Shigella strains.
  Journal
Infect Immun 63:4721-8 (1995)
Reference
PMID:7665485
  Authors
Nakayama S, Watanabe H
  Title
Involvement of cpxA, a sensor of a two-component regulatory system, in the pH-dependent regulation of expression of Shigella sonnei virF gene.
  Journal
J Bacteriol 177:5062-9 (1995)
DOI:10.1128/JB.177.17.5062-5069.1995
Reference
PMID:8376337
  Authors
Menard R, Sansonetti PJ, Parsot C
  Title
Nonpolar mutagenesis of the ipa genes defines IpaB, IpaC, and IpaD as effectors of Shigella flexneri entry into epithelial cells.
  Journal
J Bacteriol 175:5899-906 (1993)
DOI:10.1128/JB.175.18.5899-5906.1993
Reference
PMID:8642302
  Authors
Watarai M, Funato S, Sasakawa C
  Title
Interaction of Ipa proteins of Shigella flexneri with alpha5beta1 integrin promotes entry of the bacteria into mammalian cells.
  Journal
J Exp Med 183:991-9 (1996)
DOI:10.1084/jem.183.3.991
Reference
PMID:9176079
  Authors
Fasano A, Noriega FR, Liao FM, Wang W, Levine MM
  Title
Effect of shigella enterotoxin 1 (ShET1) on rabbit intestine in vitro and in vivo.
  Journal
Gut 40:505-11 (1997)
DOI:10.1136/gut.40.4.505
Reference
  Authors
Tran Van Nhieu G, Caron E, Hall A, Sansonetti PJ
  Title
IpaC induces actin polymerization and filopodia formation during Shigella entry into epithelial cells.
  Journal
EMBO J 18:3249-62 (1999)
DOI:10.1093/emboj/18.12.3249
Reference
  Authors
Egile C, Loisel TP, Laurent V, Li R, Pantaloni D, Sansonetti PJ, Carlier MF
  Title
Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility.
  Journal
J Cell Biol 146:1319-32 (1999)
DOI:10.1083/jcb.146.6.1319
Reference
  Authors
Skoudy A, Mounier J, Aruffo A, Ohayon H, Gounon P, Sansonetti P, Tran Van Nhieu G
  Title
CD44 binds to the Shigella IpaB protein and participates in bacterial invasion of epithelial cells.
  Journal
Cell Microbiol 2:19-33 (2000)
DOI:10.1046/j.1462-5822.2000.00028.x
Reference
  Authors
Pantaloni D, Le Clainche C, Carlier MF
  Title
Mechanism of actin-based motility.
  Journal
Science 292:1502-6 (2001)
DOI:10.1126/science.1059975
Reference
  Authors
Yoshida S, Katayama E, Kuwae A, Mimuro H, Suzuki T, Sasakawa C
  Title
Shigella deliver an effector protein to trigger host microtubule destabilization, which promotes Rac1 activity and efficient bacterial internalization.
  Journal
EMBO J 21:2923-35 (2002)
DOI:10.1093/emboj/cdf319
Reference
  Authors
Niebuhr K, Giuriato S, Pedron T, Philpott DJ, Gaits F, Sable J, Sheetz MP, Parsot C, Sansonetti PJ, Payrastre B
  Title
Conversion of PtdIns(4,5)P(2) into PtdIns(5)P by the S.flexneri effector IpgD reorganizes host cell morphology.
  Journal
EMBO J 21:5069-78 (2002)
DOI:10.1093/emboj/cdf522
Reference
  Authors
Hume PJ, McGhie EJ, Hayward RD, Koronakis V
  Title
The purified Shigella IpaB and Salmonella SipB translocators share biochemical properties and membrane topology.
  Journal
Mol Microbiol 49:425-39 (2003)
DOI:10.1046/j.1365-2958.2003.03559.x
Reference
  Authors
Sossey-Alaoui K, Head K, Nowak N, Cowell JK
  Title
Genomic organization and expression profile of the human and mouse WAVE gene family.
  Journal
Mamm Genome 14:314-22 (2003)
DOI:10.1007/s00335-002-2247-7
Reference
  Authors
Cherla RP, Lee SY, Tesh VL
  Title
Shiga toxins and apoptosis.
  Journal
FEMS Microbiol Lett 228:159-66 (2003)
DOI:10.1016/S0378-1097(03)00761-4
Reference
  Authors
Cossart P, Sansonetti PJ
  Title
Bacterial invasion: the paradigms of enteroinvasive pathogens.
  Journal
Science 304:242-8 (2004)
DOI:10.1126/science.1090124
Reference
  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
Reference
  Authors
Nhieu GT, Enninga J, Sansonetti P, Grompone G
  Title
Tyrosine kinase signaling and type III effectors orchestrating Shigella invasion.
  Journal
Curr Opin Microbiol 8:16-20 (2005)
DOI:10.1016/j.mib.2004.12.006
Reference
  Authors
Picking WL, Nishioka H, Hearn PD, Baxter MA, Harrington AT, Blocker A, Picking WD
  Title
IpaD of Shigella flexneri is independently required for regulation of Ipa protein secretion and efficient insertion of IpaB and IpaC into host membranes.
  Journal
Infect Immun 73:1432-40 (2005)
DOI:10.1128/IAI.73.3.1432-1440.2005
Reference
  Authors
Okuda J, Toyotome T, Kataoka N, Ohno M, Abe H, Shimura Y, Seyedarabi A, Pickersgill R, Sasakawa C
  Title
Shigella effector IpaH9.8 binds to a splicing factor U2AF(35) to modulate host immune responses.
  Journal
Biochem Biophys Res Commun 333:531-9 (2005)
DOI:10.1016/j.bbrc.2005.05.145
Reference
  Authors
Kim DW, Lenzen G, Page AL, Legrain P, Sansonetti PJ, Parsot C
  Title
The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes.
  Journal
Proc Natl Acad Sci U S A 102:14046-51 (2005)
DOI:10.1073/pnas.0504466102
Reference
  Authors
Alto NM, Shao F, Lazar CS, Brost RL, Chua G, Mattoo S, McMahon SA, Ghosh P, Hughes TR, Boone C, Dixon JE
  Title
Identification of a bacterial type III effector family with G protein mimicry functions.
  Journal
Cell 124:133-45 (2006)
DOI:10.1016/j.cell.2005.10.031
Reference
  Authors
Ogawa M, Sasakawa C
  Title
Intracellular survival of Shigella.
  Journal
Cell Microbiol 8:177-84 (2006)
DOI:10.1111/j.1462-5822.2005.00652.x
Reference
  Authors
Miura M, Terajima J, Izumiya H, Mitobe J, Komano T, Watanabe H
  Title
OspE2 of Shigella sonnei is required for the maintenance of cell architecture of bacterium-infected cells.
  Journal
Infect Immun 74:2587-95 (2006)
DOI:10.1128/IAI.74.5.2587-2595.2006
Reference
  Authors
Hilbi H
  Title
Modulation of phosphoinositide metabolism by pathogenic bacteria.
  Journal
Cell Microbiol 8:1697-706 (2006)
DOI:10.1111/j.1462-5822.2006.00793.x
Reference
  Authors
Demali KA, Jue AL, Burridge K
  Title
IpaA targets beta1 integrins and rho to promote actin cytoskeleton rearrangements necessary for Shigella entry.
  Journal
J Biol Chem 281:39534-41 (2006)
DOI:10.1074/jbc.M605939200
Reference
  Authors
Yoshida S, Handa Y, Suzuki T, Ogawa M, Suzuki M, Tamai A, Abe A, Katayama E, Sasakawa C
  Title
Microtubule-severing activity of Shigella is pivotal for intercellular spreading.
  Journal
Science 314:985-9 (2006)
DOI:10.1126/science.1133174
Reference
  Authors
Handa Y, Suzuki M, Ohya K, Iwai H, Ishijima N, Koleske AJ, Fukui Y, Sasakawa C
  Title
Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery.
  Journal
Nat Cell Biol 9:121-8 (2007)
DOI:10.1038/ncb1526
Reference
  Authors
Mattoo S, Lee YM, Dixon JE
  Title
Interactions of bacterial effector proteins with host proteins.
  Journal
Curr Opin Immunol 19:392-401 (2007)
DOI:10.1016/j.coi.2007.06.005
Reference
  Authors
Iwai H, Kim M, Yoshikawa Y, Ashida H, Ogawa M, Fujita Y, Muller D, Kirikae T, Jackson PK, Kotani S, Sasakawa C
  Title
A bacterial effector targets Mad2L2, an APC inhibitor, to modulate host cell cycling.
  Journal
Cell 130:611-23 (2007)
DOI:10.1016/j.cell.2007.06.043
Reference
  Authors
Rohde JR, Breitkreutz A, Chenal A, Sansonetti PJ, Parsot C
  Title
Type III secretion effectors of the IpaH family are E3 ubiquitin ligases.
  Journal
Cell Host Microbe 1:77-83 (2007)
DOI:10.1016/j.chom.2007.02.002
Reference
  Authors
Zhang J, Shao F, Li Y, Cui H, Chen L, Li H, Zou Y, Long C, Lan L, Chai J, Chen S, Tang X, Zhou JM
  Title
A Pseudomonas syringae effector inactivates MAPKs to suppress PAMP-induced immunity in plants.
  Journal
Cell Host Microbe 1:175-85 (2007)
DOI:10.1016/j.chom.2007.03.006
Reference
  Authors
Mounier J, Popoff MR, Enninga J, Frame MC, Sansonetti PJ, Van Nhieu GT
  Title
The IpaC carboxyterminal effector domain mediates Src-dependent actin polymerization during Shigella invasion of epithelial cells.
  Journal
PLoS Pathog 5:e1000271 (2009)
DOI:10.1371/journal.ppat.1000271
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