KEGG   PATHWAY: hsa05131Help
Entry
hsa05131                    Pathway                                

Name
Shigellosis - Homo sapiens (human)
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
Human Diseases; Infectious diseases
BRITE hierarchy
Pathway map
Shigellosis
hsa05131

All organismsOrtholog table
Disease
H00299  
Shigellosis
Organism
Homo sapiens (human) [GN:hsa]
Gene
3678  
ITGA5; integrin subunit alpha 5 [KO:K06484]
3688  
ITGB1; integrin subunit beta 1 [KO:K05719]
960  
CD44; CD44 molecule (Indian blood group) [KO:K06256]
391  
RHOG; ras homolog family member G [KO:K07863]
9844  
ELMO1; engulfment and cell motility 1 [KO:K12366]
63916  
ELMO2; engulfment and cell motility 2 [KO:K18985]
79767  
ELMO3; engulfment and cell motility 3 [KO:K19241]
1793  
DOCK1; dedicator of cytokinesis 1 [KO:K13708]
5879  
RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
8936  
WASF1; WAS protein family member 1 [KO:K05753]
10163  
WASF2; WAS protein family member 2 [KO:K05748]
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]
10093  
ARPC4; actin related protein 2/3 complex subunit 4 [KO:K05755]
10094  
ARPC3; actin related protein 2/3 complex subunit 3 [KO:K05756]
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]
6714  
SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
2017  
CTTN; cortactin [KO:K06106]
3059  
HCLS1; hematopoietic cell-specific Lyn substrate 1 [KO:K06106]
25  
ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
1398  
CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
1399  
CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
998  
CDC42; cell division cycle 42 [KO:K04393]
7414  
VCL; vinculin [KO:K05700]
1729  
DIAPH1; diaphanous related formin 1 [KO:K05740]
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]
7454  
WAS; Wiskott-Aldrich syndrome [KO:K05747]
8976  
WASL; Wiskott-Aldrich syndrome like [KO:K05747]
60  
ACTB; actin beta [KO:K05692]
71  
ACTG1; actin gamma 1 [KO:K05692]
345456  
PFN3; profilin 3 [KO:K05759]
5216  
PFN1; profilin 1 [KO:K05759]
5217  
PFN2; profilin 2 [KO:K05759]
375189  
PFN4; profilin family member 4 [KO:K05759]
9474  
ATG5; autophagy related 5 [KO:K08339]
10392  
NOD1; nucleotide binding oligomerization domain containing 1 [KO:K08727]
64127  
NOD2; nucleotide binding oligomerization domain containing 2 [KO:K10165]
8767  
RIPK2; receptor interacting serine/threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
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]
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]
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]
8517  
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
4793  
NFKBIB; NFKB inhibitor beta [KO:K02581]
4792  
NFKBIA; NFKB inhibitor alpha [KO:K04734]
4790  
NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  
RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
3576  
CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
7307  
U2AF1; U2 small nuclear RNA auxiliary factor 1 [KO:K12836]
U2AF1L5; U2 small nuclear RNA auxiliary factor 1 like 5 [KO:K12836]
199746  
U2AF1L4; U2 small nuclear RNA auxiliary factor 1 like 4 [KO:K12836]
8945  
BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
23291  
FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
10459  
MAD2L2; MAD2 mitotic arrest deficient-like 2 (yeast) [KO:K13728]
7322  
UBE2D2; ubiquitin conjugating enzyme E2 D2 [KO:K06689] [EC:2.3.2.23]
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)
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)
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)
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)
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)
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)
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)
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)
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)
Reference
  Authors
Pantaloni D, Le Clainche C, Carlier MF
  Title
Mechanism of actin-based motility.
  Journal
Science 292:1502-6 (2001)
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)
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)
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)
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)
Reference
  Authors
Cherla RP, Lee SY, Tesh VL
  Title
Shiga toxins and apoptosis.
  Journal
FEMS Microbiol Lett 228:159-66 (2003)
Reference
  Authors
Cossart P, Sansonetti PJ
  Title
Bacterial invasion: the paradigms of enteroinvasive pathogens.
  Journal
Science 304:242-8 (2004)
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)
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)
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)
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)
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)
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)
Reference
  Authors
Ogawa M, Sasakawa C
  Title
Intracellular survival of Shigella.
  Journal
Cell Microbiol 8:177-84 (2006)
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)
Reference
  Authors
Hilbi H
  Title
Modulation of phosphoinositide metabolism by pathogenic bacteria.
  Journal
Cell Microbiol 8:1697-706 (2006)
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)
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)
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)
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)
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)
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)
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)
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)
KO pathway
 

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