Conserved regulation of omptin proteases by the PhoPQ two-component regulatory system in Enterobacteriaceae.

Bacteria that colonize eukaryotic surfaces interact with numerous host-produced molecules that have antimicrobial activity. Bacteria have evolved numerous strategies to both detect and resist these molecules, and in gram-negative bacteria these include alterations of the cell surface lipopolysaccharide structure and/or charge and the production of proteases that can degrade these antimicrobial molecules. Many of the lipopolysaccharide alterations found in enteric bacteria are controlled by the PhoPQ and PmrAB two-component regulatory systems. Here, we show that omptin family proteases from Escherichia coli and Citrobacter rodentium are induced by growth in low Mg2+. We further show that deletion of PhoP eliminates omptin protease activity, transcriptional regulation and protein levels. We identify conserved PhoP-binding sites in the promoters of the E. coli omptin genes, ompT, ompP and arlC as well as in croP of Citrobacter rodentium and show that mutation of the putative PhoP-binding site in the ompT promoter abrogates PhoP-dependent expression. Finally, we show that despite the conserved PhoP-dependent regulation, each of the E. coli omptin proteins has differential activity toward a particular substrate, suggesting that each omptin may contribute to resistance to a particular repertoire of host-defense peptides, depending on the particular environment in which each evolved.