KEGG   PATHWAY: ko05131
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
Human Diseases; Infectious disease: bacterial
Pathway map
ko05131  Shigellosis
ko05131

Module
M00363  EHEC pathogenicity signature, Shiga toxin [PATH:ko05131]
Disease
H00299  Shigellosis
Orthology
K00844  HK; hexokinase [EC:2.7.1.1]
K00914  PIK3C3, VPS34; phosphatidylinositol 3-kinase [EC:2.7.1.137]
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01116  PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K01367  CAPN1; calpain-1 [EC:3.4.22.52]
K01370  CASP1; caspase 1 [EC:3.4.22.36]
K02159  BAX; apoptosis regulator BAX
K02161  BCL2; apoptosis regulator Bcl-2
K02406  fliC, hag; flagellin
K02580  NFKB1; nuclear factor NF-kappa-B p105 subunit
K02581  NFKBIB; NF-kappa-B inhibitor beta
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02861  RIPK1, RIP1; receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1]
K02927  RP-L40e, RPL40, UBA52; ubiquitin-large subunit ribosomal protein L40e
K02977  RP-S27Ae, RPS27A, UBA80; ubiquitin-small subunit ribosomal protein S27Ae
K03083  GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26]
K03094  SKP1, CBF3D; S-phase kinase-associated protein 1
K03156  TNF, TNFA; tumor necrosis factor superfamily, member 2
K03158  TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A
K03171  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein
K03173  TRAF2; TNF receptor-associated factor 2 [EC:2.3.2.27]
K03175  TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]
K03221  yscF, sctF, ssaG, prgI; type III secretion protein F
K03347  CUL1, CDC53; cullin 1
K03362  FBXW1_11, BTRC, beta-TRCP; F-box and WD-40 domain protein 1/11
K03853  CAPN2; calpain-2 [EC:3.4.22.53]
K03868  RBX1, ROC1; E3 ubiquitin-protein ligase RBX1 [EC:2.3.2.32]
K03990  C3; complement component 3
K04281  CAST; calpastatin
K04361  EGFR, ERBB1; epidermal growth factor receptor [EC:2.7.10.1]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04386  IL1R1, CD121a; interleukin 1 receptor type I
K04391  CD14; monocyte differentiation antigen CD14
K04392  RAC1; Ras-related C3 botulinum toxin substrate 1
K04393  CDC42; cell division control protein 42
K04394  CASP4, CASP11; caspase 4 [EC:3.4.22.57 3.4.22.64]
K04403  MAP3K7IP1, TAB1; TAK1-binding protein 1
K04404  MAP3K7IP2, TAB2; TAK1-binding protein 2
K04427  MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]
K04438  CRK, CRKII; C-crk adapter molecule crk
K04440  JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04441  P38; p38 MAP kinase [EC:2.7.11.24]
K04445  RPS6KA5, MSK1; ribosomal protein S6 kinase alpha-5 [EC:2.7.11.1]
K04448  JUN; transcription factor AP-1
K04451  TP53, P53; tumor protein p53
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04467  IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K04513  RHOA; Ras homolog gene family, member A
K04514  ROCK1; Rho-associated protein kinase 1 [EC:2.7.11.39]
K04519  IL1B; interleukin 1 beta
K04551  UBB; ubiquitin B
K04570  BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04688  RPS6KB; ribosomal protein S6 kinase beta [EC:2.7.11.1]
K04728  ATM, TEL1; serine-protein kinase ATM [EC:2.7.11.1]
K04729  MYD88; myeloid differentiation primary response protein MyD88
K04734  NFKBIA; NF-kappa-B inhibitor alpha
K04735  RELA; transcription factor p65
K04958  ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959  ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960  ITPR3; inositol 1,4,5-triphosphate receptor type 3
K05410  TBK1; TANK-binding kinase 1 [EC:2.7.11.10]
K05411  IRF3; interferon regulatory factor 3
K05415  IFNB; interferon beta
K05427  CSF2, GMCSF; granulocyte-macrophage colony-stimulating factor
K05482  IL18, IL1F4; interleukin 18
K05692  ACTB_G1; actin beta/gamma 1
K05699  ACTN1_4; actinin alpha 1/4
K05700  VCL; vinculin
K05704  SRC; tyrosine-protein kinase Src [EC:2.7.10.2]
K05719  ITGB1, CD29; integrin beta 1
K05725  PTK2, FAK; focal adhesion kinase 1 [EC:2.7.10.2]
K05726  BCAR1, CAS; breast cancer anti-estrogen resistance 1
K05740  DIAPH1; diaphanous 1
K05748  WASF2; WAS protein family, member 2
K05753  WASF1; WAS protein family, member 1
K05754  ARPC5; actin related protein 2/3 complex, subunit 5
K05755  ARPC4; actin related protein 2/3 complex, subunit 4
K05756  ARPC3; actin related protein 2/3 complex, subunit 3
K05757  ARPC1A_B; actin related protein 2/3 complex, subunit 1A/1B
K05758  ARPC2; actin related protein 2/3 complex, subunit 2
K05759  PFN; profilin
K05760  PXN; paxillin
K05857  PLCD; phosphatidylinositol phospholipase C, delta [EC:3.1.4.11]
K05858  PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K05859  PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11]
K05860  PLCE; phosphatidylinositol phospholipase C, epsilon [EC:3.1.4.11]
K05861  PLCZ; phosphatidylinositol phospholipase C, zeta [EC:3.1.4.11]
K05862  VDAC1; voltage-dependent anion channel protein 1
K05864  PPID, CYPD; peptidyl-prolyl isomerase D [EC:5.2.1.8]
K06068  PRKCD; novel protein kinase C delta type [EC:2.7.11.13]
K06106  CTTN, EMS1; cortactin
K06256  CD44; CD44 antigen
K06271  TLN; talin
K06272  ILK; integrin-linked kinase [EC:2.7.11.1]
K06484  ITGA5, CD49e; integrin alpha 5
K06643  MDM2; E3 ubiquitin-protein ligase Mdm2 [EC:2.3.2.27]
K06689  UBE2D, UBC4, UBC5; ubiquitin-conjugating enzyme E2 D [EC:2.3.2.23]
K07201  FOXO1; forkhead box protein O1
K07203  MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1]
K07204  RAPTOR; regulatory associated protein of mTOR
K07209  IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07345  fimA; major type 1 subunit fimbrin (pilin)
K07368  BCL10; B-cell CLL/lymphoma 10
K07369  MALT1; mucosa-associated lymphoid tissue lymphoma translocation protein 1 [EC:3.4.22.-]
K07937  ARF1_2; ADP-ribosylation factor 1/2
K07941  ARF6; ADP-ribosylation factor 6
K08333  PIK3R4, VPS15; phosphoinositide-3-kinase, regulatory subunit 4 [EC:2.7.11.1]
K08334  BECN, VPS30, ATG6; beclin
K08336  ATG12; ubiquitin-like protein ATG12
K08339  ATG5; autophagy-related protein 5
K08583  CAPNS1, CAPN4; calpain, small subunit 1
K08727  NOD1, CARD4; nucleotide-binding oligomerization domain-containing protein 1
K08738  CYC; cytochrome c
K08770  UBC; ubiquitin C
K08822  GSK3A; glycogen synthase kinase 3 alpha [EC:2.7.11.26]
K08846  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [EC:2.7.11.1]
K09408  FOXO3; forkhead box protein O3
K09849  TRAF5; TNF receptor-associated factor 5
K10030  IL8, CXCL8; interleukin 8
K10160  TLR4, CD284; toll-like receptor 4
K10168  TLR5; toll-like receptor 5
K10351  MYL2; myosin regulatory light chain 2
K10435  MAP1LC; microtubule-associated protein 1 light chain
K10580  UBE2N, BLU, UBC13; ubiquitin-conjugating enzyme E2 N [EC:2.3.2.23]
K10630  RBCK1, HOIL1; RanBP-type and C3HC4-type zinc finger-containing protein 1 [EC:2.3.2.31]
K10704  UBE2V; ubiquitin-conjugating enzyme E2 variant
K11006  stxA; shiga toxin subunit A
K11007  stxB; shiga toxin subunit B
K11011  set1A; enterotoxin Set1A
K11012  set1B; enterotoxin Set1B
K11253  H3; histone H3
K11586  CBX3, HP1G; chromobox protein 3
K11974  RNF31, HOIP; E3 ubiquitin-protein ligase RNF31 [EC:2.3.2.31]
K12358  FOXO4; forkhead box protein O4
K12366  ELMO1, CED12; engulfment and cell motility protein 1
K12499  CCL5; C-C motif chemokine 5
K12654  STING1, TMEM173, MITA; stimulator of interferon genes protein
K12679  icsA, virG; outer membrane protein IcsA
K12753  MYL5; myosin regulatory light chain 5
K12754  MYL7; myosin regulatory light chain 7
K12755  MYL9; myosin regulatory light chain 9
K12756  MYL10; myosin regulatory light chain 10
K12757  MYL12; myosin regulatory light chain 12
K12758  MYLPF; fast skeletal myosin light chain 2
K12785  espG, virA; LEE-encoded effector EspG
K12791  ARHGEF2, GEF-H1; Rho guanine nucleotide exchange factor 2
K12793  MAP3K7IP3, TAB3; TAK1-binding protein 3
K12799  PYCARD, ASC; apoptosis-associated speck-like protein containing a CARD
K12800  NLRP3, PYPAF1; NACHT, LRR and PYD domains-containing protein 3
K12805  NLRC4, CARD12; NLR family CARD domain-containing protein 4
K12807  NAIP, BIRC1; baculoviral IAP repeat-containing protein 1
K12836  U2AF1; splicing factor U2AF 35 kDa subunit
K13085  ipgD, sopB; phosphatidylinositol-4,5-bisphosphate 4-phosphatase [EC:3.1.3.78]
K13284  sipA, ipaA; invasin A
K13285  sipB, ipaB, bipB; invasin B
K13286  sipC, ipaC, bipC; invasin C
K13287  sipD, ipaD, bipD; invasin D
K13450  ospF, mkaD, spvC; phosphothreonine lyase [EC:4.2.3.-]
K13520  icsP, sopA; outer membrane protease [EC:3.4.23.-]
K13708  DOCK1; dedicator of cytokinesis protein 1
K13742  ipgB1; protein IpgB1
K13743  ipgB2; protein IpgB2
K13790  icsB, bopA; virulence protein IcsB
K13791  ipaH9.8; invasion plasmid antigen
K13792  ospG; secreted effector OspG
K13793  ospE, espO; secreted effector OspE
K14381  SQSTM1; sequestosome 1
K15464  BNIP3; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3
K16184  AKT1S1, PRAS40; proline-rich AKT1 substrate 1
K16185  RRAGA_B; Ras-related GTP-binding protein A/B
K16186  RRAGC_D; Ras-related GTP-binding protein C/D
K16938  SEPT3_9_12; septin 3/9/12
K16939  SEPT6_8_11; septin 6/8/11
K16942  SEPT2; septin 2
K16944  SEPT7, CDC3; septin 7
K17260  ACTR2, ARP2; actin-related protein 2
K17388  ROCK2; Rho-associated protein kinase 2 [EC:2.7.11.39]
K17834  CGAS, MB21D1; cyclic GMP-AMP synthase [EC:2.7.7.86]
K17847  FOXO6; forkhead box protein O6
K17889  ATG14L, ATG14; beclin 1-associated autophagy-related key regulator
K17890  ATG16L1; autophagy-related protein 16-1
K17908  WIPI1_2, ATG18; autophagy-related protein 18
K17988  TECPR1; tectonin beta-propeller repeat-containing protein 1
K18050  PRKCE; novel protein kinase C epsilon type [EC:2.7.11.13]
K18052  PRKCQ; novel protein kinase C theta type [EC:2.7.11.13]
K18441  CYTH; cytohesin
K18584  ACTR3, ARP3; actin-related protein 3
K18985  ELMO2, CED12A; engulfment and cell motility protein 2
K20121  FNBP1; formin-binding protein 1
K20894  SHARPIN; shank-associated RH domain-interacting protein
K21348  CALCOCO2, NDP52; calcium-binding and coiled-coil domain-containing protein 2
K22487  prgJ; type III secretion system protein
K23345  GLMN; glomulin
K23612  WASL; neural Wiskott-Aldrich syndrome protein
K23654  nleE, ospZ; T3SS secreted effector NleE
K23826  TIFA; TRAF-interacting protein with FHA domain-containing protein A
K23827  ospI; glutamine deamidase
K23828  ipaH1.4_2.5; E3 ubiquitin-protein ligase IpaH1.4/2.5
K23829  TNIP1, ABIN1; TNFAIP3-interacting protein 1
K23830  ipaH4.5; E3 ubiquitin-protein ligase IpaH4.5
K23831  ipaH0722; E3 ubiquitin-protein ligase IpaH0722
K23832  ipaJ; cysteine protease IpaJ
K23833  ospC; secreted effector OspC
K23834  ipaH7.8; E3 ubiquitin-protein ligase IpaH7.8
Compound
C00076  Calcium cation
C00123  L-Leucine
C00165  Diacylglycerol
C00238  Potassium cation
C00338  Lipopolysaccharide
C00407  L-Isoleucine
C01245  D-myo-Inositol 1,4,5-trisphosphate
C04549  1-Phosphatidyl-1D-myo-inositol 3-phosphate
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
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C11472  D-glycero-beta-D-manno-Heptose 1,7-bisphosphate
C11557  1-Phosphatidyl-1D-myo-inositol 5-phosphate
C20640  Cyclic GMP-AMP
Reference
PMID:30953429
  Authors
Schnupf P, Sansonetti PJ
  Title
Shigella Pathogenesis: New Insights through Advanced Methodologies.
  Journal
Microbiol Spectr 7:BAI-0023-2019 (2019)
DOI:10.1128/microbiolspec.BAI-0023-2019
Reference
PMID:28393050
  Authors
Mattock E, Blocker AJ
  Title
How Do the Virulence Factors of Shigella Work Together to Cause Disease?
  Journal
Front Cell Infect Microbiol 7:64 (2017)
DOI:10.3389/fcimb.2017.00064
Reference
PMID:25999954
  Authors
Ashida H, Mimuro H, Sasakawa C
  Title
Shigella manipulates host immune responses by delivering effector proteins with specific roles.
  Journal
Front Immunol 6:219 (2015)
DOI:10.3389/fimmu.2015.00219
Reference
PMID:20228623
  Authors
Sasakawa C
  Title
A new paradigm of bacteria-gut interplay brought through the study of Shigella.
  Journal
Proc Jpn Acad Ser B Phys Biol Sci 86:229-43 (2010)
DOI:10.2183/pjab.86.229
Reference
PMID:25264025
  Authors
Ashida H, Kim M, Sasakawa C
  Title
Manipulation of the host cell death pathway by Shigella.
  Journal
Cell Microbiol 16:1757-66 (2014)
DOI:10.1111/cmi.12367
Reference
PMID:29875765
  Authors
Siqueira MDS, Ribeiro RM, Travassos LH
  Title
Autophagy and Its Interaction With Intracellular Bacterial Pathogens.
  Journal
Front Immunol 9:935 (2018)
DOI:10.3389/fimmu.2018.00935
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
Related
pathway
ko03070  Bacterial secretion system
ko04010  MAPK signaling pathway
ko04064  NF-kappa B signaling pathway
ko04140  Autophagy - animal
ko04210  Apoptosis
ko04510  Focal adhesion
ko04621  NOD-like receptor signaling pathway
ko04623  Cytosolic DNA-sensing pathway
ko04810  Regulation of actin cytoskeleton

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