Working model for PreA/PreB regulation of pmrCAB. (A) The genes pmrCAB and yibD are part of the PmrA regulon. Extracellular signals that affect the PreB sensor are unknown, but growth in LB medium activates its phosphatase activity, maintaining the PreA response regulator in the unphosphorylated conformation. In a PreB[H246G] background, PreA is also inactivated by the phosphatase activity of the mutant protein. (B) Under PreA/PreB-inducing conditions not yet identified, PreA indirectly regulates pmrCAB and yibD. (C) Ectopic PreA, but not PreA[D51A], can activate pmrCAB in a ΔpreB mutant even when grown in LB medium, presumably because of signal-independent cellular cross talk, which may become unmasked and more important due to the absence of the cognate sensor protein.