Entry Name Vibrio cholerae infection
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.
Class Human Diseases; Infectious disease: bacterialBRITE hierarchy
Pathway map Module M00850 Vibrio cholerae pathogenicity signature, cholera toxins [PATH:ko05110 ]
M00852 Vibrio cholerae pathogenicity signature, toxin coregulated pilus [PATH:ko05110 ]
Disease Orthology K01116 PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11 ]
K02144 ATPeV1H; V-type H+-transporting ATPase subunit H
K02145 ATPeV1A, ATP6A; V-type H+-transporting ATPase subunit A [EC:7.1.2.2 ]
K02146 ATPeV0D, ATP6D; V-type H+-transporting ATPase subunit d
K02147 ATPeV1B, ATP6B; V-type H+-transporting ATPase subunit B
K02148 ATPeV1C, ATP6C; V-type H+-transporting ATPase subunit C
K02149 ATPeV1D, ATP6M; V-type H+-transporting ATPase subunit D
K02150 ATPeV1E, ATP6E; V-type H+-transporting ATPase subunit E
K02151 ATPeV1F, ATP6S14; V-type H+-transporting ATPase subunit F
K02152 ATPeV1G, ATP6G; V-type H+-transporting ATPase subunit G
K02153 ATPeV0E, ATP6H; V-type H+-transporting ATPase subunit e
K02154 ATPeV0A, ATP6N; V-type H+-transporting ATPase subunit a
K02155 ATPeV0C, ATP6L; V-type H+-transporting ATPase 16kDa proteolipid subunit
K03661 ATPeV0B, ATP6F; V-type H+-transporting ATPase 21kDa proteolipid subunit
K03662 ATPeVS1, ATP6S1; V-type H+-transporting ATPase S1 subunit
K04632 GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K04926 KCNQ1, KV7.1; potassium voltage-gated channel KQT-like subfamily member 1
K05031 CFTR, ABCC7; cystic fibrosis transmembrane conductance regulator [EC:5.6.1.6 ]
K05692 ACTB_G1; actin beta/gamma 1
K05701 TJP1, ZO1; tight junction protein 1
K05859 PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11 ]
K06098 TJP2, ZO2; tight junction protein 2
K07342 SEC61G, SSS1, secE; protein transport protein SEC61 subunit gamma and related proteins
K07937 ARF1_2; ADP-ribosylation factor 1/2
K09481 SEC61B, SBH2; protein transport protein SEC61 subunit beta
K10929 ctxB; cholera enterotoxin subunit B
K10930 tcpA; toxin coregulated pilin
K10931 tcpB; toxin coregulated pilus biosynthesis protein B
K10932 tcpC; toxin coregulated pilus biosynthesis outer membrane protein C
K10933 tcpD; toxin coregulated pilus biosynthesis protein D
K10934 tcpE; toxin coregulated pilus biosynthesis protein E
K10935 tcpF; toxin coregulated pilus biosynthesis protein F
K10949 KDELR; ER lumen protein retaining receptor
K10950 ERO1L; ERO1-like protein alpha [EC:1.8.4.-]
K10951 SLC12A2, NKCC1; solute carrier family 12 (sodium/potassium/chloride transporter), member 2
K10952 ace; accessory cholera enterotoxin
K10954 zot; zona occludens toxin
K10956 SEC61A; protein transport protein SEC61 subunit alpha
K21712 gbpA; N-acetylglucosamine-binding protein A
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
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 Reference Authors Fullner KJ, Mekalanos JJ.
Title In vivo covalent cross-linking of cellular actin by the Vibrio cholerae RTX toxin.
Journal 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 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 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 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 Reference Authors Fasano A.
Title Toxins and the gut: role in human disease.
Journal Reference Authors Uzzau S, Fasano A.
Title Cross-talk between enteric pathogens and the intestine.
Journal Reference Authors Sandkvist M.
Title Type II secretion and pathogenesis.
Journal Reference Authors Field M.
Title Intestinal ion transport and the pathophysiology of diarrhea.
Journal Reference Authors Lencer WI, Tsai B.
Title The intracellular voyage of cholera toxin: going retro.
Journal Reference Authors De Haan L, Hirst TR.
Title Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (Review).
Journal Reference Authors Chinnapen DJ, Chinnapen H, Saslowsky D, Lencer WI.
Title Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER.
Journal Reference Authors Sheahan KL, Cordero CL, Satchell KJ.
Title Autoprocessing of the Vibrio cholerae RTX toxin by the cysteine protease domain.
Journal Reference Authors Fasano A.
Title Intestinal zonulin: open sesame!
Journal Related ko05111 Biofilm formation - Vibrio cholerae
