KEGG   PATHWAY: vch05110
Entry
vch05110                    Pathway                                
Name
Vibrio cholerae infection - Vibrio cholerae O1 El Tor N16961
Description
Cholera toxin (CTX) is one of the main virulence factors of Vibrio cholerae. Once secreted, CTX B-chain (CTXB) binds to ganglioside GM1 on the surface of the host's cells. After binding takes place, the entire CTX complex is carried from plasma membrane (PM) to endoplasmic reticulum (ER). In the ER, the A-chain (CTXA) is recognized by protein disulfide isomerase (PDI), unfolded, and delivered to the membrane where the membrane-associated ER-oxidase, Ero1, oxidizes PDI to release the CTXA into the protein-conducting channel, Sec61. CTXA is then retro-translocated to the cytosol and induces water and electrolyte secretion by increasing cAMP levels via adenylate cyclase (AC) to exert toxicity.
Other than CTX, Vibrio cholerae generates several toxins that are perilous to eukaryotic cells. Zonula occludens toxin (ZOT) causes tight junction disruption through protein kinase C-dependent actin polymerization. RTX toxin (RtxA) causes actin depolymerization by covalently cross-linking actin monomers into dimers, trimers, and higher multimers. Vibrio cholerae cytolysin (VCC) is an important pore-forming toxin. The assembly of VCC anion channels in cells cause vacuolization and lysis.
Class
Human Diseases; Infectious disease: bacterial
Pathway map
vch05110  Vibrio cholerae infection
vch05110

Module
vch_M00850  Vibrio cholerae pathogenicity signature, cholera toxins [PATH:vch05110]
vch_M00852  Vibrio cholerae pathogenicity signature, toxin coregulated pilus [PATH:vch05110]
Organism
Vibrio cholerae O1 El Tor N16961 [GN:vch]
Gene
VC_A0219  haemolysin [KO:K10948]
VC_1457  cholera enterotoxin, A subunit [KO:K10928] [EC:2.4.2.36]
VC_1456  cholera enterotoxin, B subunit [KO:K10929]
VC_1784  neuraminidase [KO:K23550] [EC:3.2.1.18]
VC_1459  accessory cholera enterotoxin [KO:K10952]
VC_1451  RTX toxin RtxA [KO:K10953]
VC_1458  zona occludens toxin [KO:K10954]
VC_0828  toxin co-regulated pilin [KO:K10930]
VC_0829  toxin co-regulated pilus biosynthesis protein B [KO:K10931]
VC_0831  toxin co-regulated pilus biosynthesis outer membrane protein C [KO:K10932]
VC_0833  toxin co-regulated pilus biosynthesis protein D [KO:K10933]
VC_0836  toxin co-regulated pilus biosynthesis protein E [KO:K10934]
VC_0837  toxin co-regulated pilus biosynthesis protein F [KO:K10935]
VC_A0811  chitinase, putative [KO:K21712]
VC_A0865  hemagglutinin/protease [KO:K08604] [EC:3.4.24.25]
Compound
C00014  Ammonia
C00080  H+
C00165  Diacylglycerol
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C00698  Cl-
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C04911  D-Galactosyl-N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
Reference
  Authors
Trucksis M, Conn TL, Wasserman SS, Sears CL.
  Title
Vibrio cholerae ACE stimulates Ca(2+)-dependent Cl(-)/HCO(3)(-) secretion in T84 cells in vitro.
  Journal
Am J Physiol Cell Physiol 279:C567-77 (2000)
DOI:10.1152/ajpcell.2000.279.3.C567
Reference
  Authors
Fullner KJ, Mekalanos JJ.
  Title
In vivo covalent cross-linking of cellular actin by the Vibrio cholerae RTX toxin.
  Journal
EMBO J 19:5315-23 (2000)
DOI:10.1093/emboj/19.20.5315
Reference
  Authors
Lencer WI.
  Title
Microbes and microbial Toxins: paradigms for microbial-mucosal toxins. V. Cholera: invasion of the intestinal epithelial barrier by a stably folded protein toxin.
  Journal
Am J Physiol Gastrointest Liver Physiol 280:G781-6 (2001)
DOI:10.1152/ajpgi.2001.280.5.G781
Reference
  Authors
Moschioni M, Tombola F, de Bernard M, Coelho A, Zitzer A, Zoratti M, Montecucco C.
  Title
The Vibrio cholerae haemolysin anion channel is required for cell vacuolation and death.
  Journal
Cell Microbiol 4:397-409 (2002)
DOI:10.1046/j.1462-5822.2002.00199.x
Reference
  Authors
Tsai B, Rapoport TA.
  Title
Unfolded cholera toxin is transferred to the ER membrane and released from protein disulfide isomerase upon oxidation by Ero1.
  Journal
J Cell Biol 159:207-16 (2002)
DOI:10.1083/jcb.200207120
Reference
  Authors
Fujinaga Y, Wolf AA, Rodighiero C, Wheeler H, Tsai B, Allen L, Jobling MG, Rapoport T, Holmes RK, Lencer WI.
  Title
Gangliosides that associate with lipid rafts mediate transport of cholera and related toxins from the plasma membrane to endoplasmic reticulm.
  Journal
Mol Biol Cell 14:4783-93 (2003)
DOI:10.1091/mbc.E03-06-0354
Reference
  Authors
Fasano A.
  Title
Toxins and the gut: role in human disease.
  Journal
Gut 50 Suppl 3:III9-14 (2002)
DOI:10.1136/gut.50.suppl_3.iii9
Reference
  Authors
Uzzau S, Fasano A.
  Title
Cross-talk between enteric pathogens and the intestine.
  Journal
Cell Microbiol 2:83-9 (2000)
DOI:10.1046/j.1462-5822.2000.00041.x
Reference
  Authors
Sandkvist M.
  Title
Type II secretion and pathogenesis.
  Journal
Infect Immun 69:3523-35 (2001)
DOI:10.1128/IAI.69.6.3523-3535.2001
Reference
  Authors
Field M.
  Title
Intestinal ion transport and the pathophysiology of diarrhea.
  Journal
J Clin Invest 111:931-43 (2003)
DOI:10.1172/JCI18326
Reference
  Authors
Lencer WI, Tsai B.
  Title
The intracellular voyage of cholera toxin: going retro.
  Journal
Trends Biochem Sci 28:639-45 (2003)
DOI:10.1016/j.tibs.2003.10.002
Reference
  Authors
De Haan L, Hirst TR.
  Title
Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (Review).
  Journal
Mol Membr Biol 21:77-92 (2004)
DOI:10.1080/09687680410001663267
Reference
  Authors
Chinnapen DJ, Chinnapen H, Saslowsky D, Lencer WI.
  Title
Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER.
  Journal
FEMS Microbiol Lett 266:129-37 (2007)
DOI:10.1111/j.1574-6968.2006.00545.x
Reference
  Authors
Sheahan KL, Cordero CL, Satchell KJ.
  Title
Autoprocessing of the Vibrio cholerae RTX toxin by the cysteine protease domain.
  Journal
EMBO J 26:2552-61 (2007)
DOI:10.1038/sj.emboj.7601700
Reference
  Authors
Fasano A.
  Title
Intestinal zonulin: open sesame!
  Journal
Gut 49:159-62 (2001)
DOI:10.1136/gut.49.2.159
Related
pathway
vch00190  Oxidative phosphorylation
vch03070  Bacterial secretion system
vch05111  Biofilm formation - Vibrio cholerae
KO pathway
ko05110   
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