Global cAMP-dependent transcriptional regulator that controls virulence gene expression by distinct cAMP-dependent and -independent mechanisms, which allow to fine tune its virulence program in response to specific host cues or environments (PubMed:20494996). Controls the expression of many regulatory targets including type II, type III and type IV secretion systems, flagellar-mediated motility, and quorum sensing systems (PubMed:9190808, PubMed:12057955, PubMed:26929300, PubMed:30761117). Transcriptional control is exerted by binding to a well-characterized consensus site (5'-ANWWTGNGAWNYAGWTCACAT) within target promoters (PubMed:17159200, PubMed:20494996, PubMed:26929300). Directly binds to the toxA upstream region to regulate exotoxin A production, to the lasR gene promoter to activate the las quorum-sensing system or to the exsA promoter to regulate type III secretion system (PubMed:9190808, PubMed:12057955, PubMed:19389782). Autoregulates as well its own expression (PubMed:20494996). Homodimer. Regulated by both cAMP and cGMP to allow differential regulation of different regulons (PubMed:12057955). Cyclic AMP is required for Vfr binding to vfr, regA, ptxR, and cpdA promoter DNA (PubMed:20494996, PubMed:25897033). Cyclic GMP instead inhibits the formation of Vfr-DNA complexes (PubMed:20494996, PubMed:25897033). Mutants show loss of twitching motility and are defective in type IV pilus assembly (PubMed:12057955). Expression of ExsA is also strongly affected in the mutant (PubMed:26929300).