Regulatory loop between the CsrA system and NhaR, a high salt/high pH regulator

In E. coli, under high pH/high salt conditions, a major Na+/H+ antiporter (NhaA) is activated to maintain an internal pH level. Its expression is induced by a specific regulator NhaR, which is also responsible for osmC and pgaA regulation. Here I report that the NhaR regulator affects the carbon storage regulatory Csr system. I found that the expression of all major components of the Csr system-CsrA regulator, CsrB and CsrC small RNAs, and the CsrB and CsrC stability were indirectly affected by nhaR mutation under stress conditions. Using a combination of experimental and in silico analyses, I concluded that the mechanism of regulation included direct and indirect activation of a two-component system (TCS) response regulator-UvrY. NhaR regulation involved interactions with the regulators H-NS and SdiA and was affected by a naturally occurring spontaneous IS5 insertion in the promoter region. A regulatory circuit was proposed and discussed.