Table 1.

Interaction of ToxRS, ToxT, TcpPH, and other virulence related proteins/genes in V. cholerae.

Protein	Action/significance
ToxR/S	Interaction of ToxR with ToxS is required for full transcriptional activation by enhancing dimerization of ToxR. ToxR is protected from degradation and alkaline pH by ToxS. break ToxRS detect and transduce signals into transcriptional regulation programs.
	Activation of CT, Tcp, Acf through ToxT. ToxR act as a coactivator by increasing transcriptional activation of toxT by promoting TcpP recruitment and/or binding to the toxT promoter.
	Directly repress ompT expression and activate ompU transcription that changes the outer-membrane porin composition. break Upregulation of OmpU is important for resistance to bile acids and antimicrobial peptides present in the host.
	Enhances TcpP binding and activation of transcription.
	ToxR-regulated tcpI and acfB function with a two-component system to regulate chemotaxis.
ToxT	Activate about eight different virulence gene promoters, including the ctxAB, tcpA and acf promoters, as part of a virulence gene regulatory cascade.
	Transcription is influenced by bile, unsaturated fatty acids and bicarbonate. break Influenced by environmental signals through VarS and VarA.
	Represses expression of MSHA.
	Transcription is regulated by ToxRS and TcpPH.
	H-NS directly represses the expression of the toxT.
TcpP	Transcription is stimulated by AphAB.
	Temperature and pH influence the levels of TcpP through intramembrane proteolysis.
	Activation is signaled by HapR.
TcpH	Required for stability of TcpP and co-expressed with tcpP as an operon. break TcpH protect TcpP against this proteolytic degradation.
AphA/B	AphA activate transcription in the presence of AphB.
	Synergistic function of AphAB activates tcpPH transcription.
	Alteration of dyad symmetry due to base pair changes in the tcpPH promoter and binding of AphB is responsible for the differential expression of virulence genes in V. cholerae classical and El Tor biotypes.
	The promoters directly activated by AphB respond to intracellular pH and anaerobiosis during the early stages of the infection.
	A main transcriptional activator of biofilm formation, virulence genes, and pH homeostasis.
	HapR represses transcription.