Cholera pathogenesis

Fig. 12. Tentative model of the signal transduction chain that links the perception of pectic fragments to defense responses in carrot cells. Abbreviations apy, heterotrimeric G protein CaM, calmodulin 4CL, 4-coumarate-CoA ligase CTX, cholera toxin FC, fusicoccine GDP-P-S and GTP-y-S, guanosine 5 -0-(2-thiodiphosphate) and guanosine 5 -0-(3-thiotriphosphate) IP3, 1,4,5-inositol trisphosphate PAL, phenylalanine ammonia-lyase PLC, phospholipase C PR, pathogenesis related PTX, pertussis toxin Rc, receptor SP, staurosporine. Activation and inhibition are symbolized by + and -respectively.

Fluid and electrolyte loss in cholera patients is closely related to elevated concentrations of cAMP, which can stimulate chloride secretion in intestinal epithelial cells (Field, 1971 Moss and Vaughan, 1988a). There is also evidence for the importance of other substances, such as prostaglandin E2 (PGE2) and 5-hydroxytryptamine (5-HT), in CT-induced secretion (Kaper et al., 1995). Nilsson et al. (1983) reported that 5-HT was released from enterochromaffin cells in the cat small intestine upon CT treatment. 5-HT could then stimulate PGE2 synthesis (Beubler etai, 1989) and activate the enteric nervous system (Ekiund et al., 1984). Cholera toxin also caused release of PGE2 into the lumen of intestinal loops in vitro (Peterson and Ochoa, 1989), via an effect on arachidonic acid formation (Peterson et al., 1990 Reit-meyer and Peterson, 1990). The contribution of these, and perhaps other, CT effects to the pathogenesis of cholera remains to be elucidated (Peterson etai, 1994). 

Finkelstein RA, LoSpalluto JJ (1969) Pathogenesis of experimental cholera Preparation and isolation of choleragen and choleragenoid. In J. Exp. Med. 130 185-202. 

The monomeric G protein Arf was named for its contribution to the pathogenesis of cholera and not for its normal function in the assembly of COP I vesicles. However, it is also required for the transport of V. cholerae A-toxin. The cholera toxin is endocytosed in caveolae vesicles that subsequently merge with lyso-somes (or are transformed into lysosomes), where the acidic pH contributes to activation of the toxin. As the toxin is transported through the Golgi and ER, it is further processed and activated. Arf forms a complex with the A-toxin that promotes its travel between compartments. The A-toxin is actually an ADP-ribosylase (an enzyme that cleaves NAD and attaches the ADP portion to a protein) (see Chapter 6, Fig. 6.14), and hence, Arf became known as the ADP-ribosylating factor. The ADP-ribosylation of proteins regulating the CFTR chloride channel leads to Dennis Veere s dehydration and diarrhea. 

---