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.