Activation of A1 subunit of cholera toxin causes increased activity of:
Ans: A (Adenylate cyclase) Ref: Textbook of Microbiology, 8th ed, Ananthanarayan and Paniker. pg: 307; Mandell, Bennett and Dolin: Principles and Practice of infectious Diseases, 6th ed., pg: 1221Explanation:Cholera Toxin (CT)Production of CT is determined by a filamentous phage integrated with the bacterial chromosome..It can also replicate as a plasmid.CT is regulated by ToxR protein.CT is a protein enterotoxin.CT is made up of:o 1 A (has 2 fragments-A1 and A2).o A1 is biologically active component.o A 2 fragment only finks the biologically active A1 to B subunit.o 5 B subunits (attaches to the GM 1 ganglioside receptors on jejunal cells).The A1 fragment causes prolonged activation of cellular adenylate cyclate and accumulation of cAMP leading to outpouring into the small intestinal lumen of large quantities of water and electrolytes and the consequent watery diarrhea.CT also increases intestinal secretion via prostaglandins and neural histamine receptors.Complications in cholera result from the massive water and electrolyte depletionThe labile toxin produced by ETEC (Enterotoxigenic E.coli) also acts by increased activity of adenylate cyclase.The Stable-toxin (ST) producing E. coli causes activation of intestinal guanyiate cyclase. Cholora Toxin || |A subunitB subunit||||A1(Active part;-A2Joins A1 and B)Binds to GM1.ganglioside receptor| ADP ribosylation of G protein|Activation of adenyl cylase|Increased cAMP|Inhibits absorption of Na+ & Cl- DiarrheaFig: Mechanism of action of cholera toxinAlso Note:Mechanism of Action of Some Important Bacterial ToxinsBacterial ToxinsMechanismHeat labile toxin of E. coliIncreased cAMPHeat stable toxin of E. coliIncreased cGMPBotulism toxinInhibit release of acetylcholine from peripheral nervesTetanus toxinInhibit release of glycine and GABA at presynaptic terminalsDiphtheriaInhibit protein synthesis by inactivating EF-2
Adenylate cyclase
Guanylate cyclase
cGMP
Na K ATPase
Vibrio