Activation of leuO by LrhA in Escherichia coli

LeuO is a conserved LysR-type transcription factor of pleiotropic function in Enterobacteria. Regulation of the leuO gene has been best studied in Escherichia coli and Salmonella enterica. Its expression is silenced by the nucleoid-associated proteins H-NS and StpA, autoregulated by LeuO, and in E. coli activated by the transcription regulator BglJ-RcsB. However, signals which induce leuO expression remain unknown. Here we show that LrhA, a conserved LysR-type transcription regulator, activates leuO in E. coli. LrhA specifically binds the leuO regulatory region and activates expression of leuO from three promoters. Activation of leuO by LrhA is synergistic with activation by BglJ-RcsB, while co-regulation by LrhA, LeuO and H-NS/StpA suggests a complex regulatory interplay. In addition, hyperactive LrhA mutants including LrhA-12DN, 221TA, 61HR/221TA and 303DG were identified. Regulation of leuO by LrhA reveals a connection between the two pleiotropic regulators LeuO and LrhA in E. coli.