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

Abstract

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 Mg 2+ . We further show that deletion of PhoP eliminates omptin protease activity, transcriptional regulation and protein levels. We identify conserved PhoPbinding 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.Introduction:

Transcriptional Regulation of the Multiple Resistance Mechanisms in Salmonella—A Review

“…The best-known TCS-inducing virulence phenotype of Salmonella is the PhoP-PhoQ system [ 116 ], including the sensor kinase (PhoP) initiating the phosphorylation process, which is required for activation of RR-PhoP transcription in response to environmental signals [ 115 ]. Activation of PhoPQ signaling determines the acquisition of resistance to cationic peptides as a result of weaker peptide binding and the variable hydrophobic nature of the membrane [ 123 ]. PhoPQ is activated by a range of external factors, i.e., low levels of bivalent cations (e.g., Mg 2+ ), low pH, the presence of CAMP, or hyperosmotic stress [ 116 , 117 , 118 ].…”