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 fromEscherichia coliandCitrobacter rodentiumare 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 theE. coliomptin genes,ompT,ompPandarlCas well as incroPofCitrobacter rodentiumand show that mutation of the putative PhoP-binding site in theompTpromoter abrogates PhoP-dependent expression. Finally, we show that despite the conserved PhoP-dependent regulation, each of theE. coliomptin 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.
