Fig. 6.

Model for V. cholerae virulence cascade signal transduction system. (A) toxTpro is repressed by H-NS proteins while V. cholerae is in the aquatic environment; (B) Upon colonization of the intestinal epithelium, bile salts bind to the ToxS pocket of mandatory ToxS-ToxR heterodimer, triggering the formation of ToxS-ToxR heterotetramers; (C) The local increase of ToxR^cyt molecules enables a multiple, cooperative binding to the toxTpro regulatory region, which results in the displacement of the H-NS proteins repressing toxT; (D) Multiple ToxR molecules bind the toxTpro and recruit the DNA to the membrane; (E) Once the DNA is attached to the membrane, TcpP can bind the toxTpro either competing with ToxR (E.I) or interacting with it through a hand-hold mechanism (E.II); (F) When TcpP is properly bound to the toxTpro regulatory region, it recruits the RNA polymerase and activates toxT transcription; (G) At the ompUpro, where no TcpP molecules are involved, ToxR molecules bind near the -35 region and recruit the RNA polymerase to facilitate ompU activation.