OmpR Phosphorylation and Its Role in Signaling and Pathogenesis This two-component system response regulator modulates multiple systems, including virulence factors and fimbriae

I n prokaryotes, the major paradigm for signal transduction is the two-component regulatory system. The first component is a sensor kinase; it is phosphorylated on a histidine residue from cytoplasmic ATP. Many of these sensor kinases are inner membrane proteins with two transmembrane domains. The second component of such systems, the response regulators, often are two-domain proteins that function as transcriptional activators or repressors. They are phosphorylated by their cognate sensor kinase on a conserved aspartic acid residue, and phosphorylation usually results in an increase in DNA binding affinity. The prototypical EnvZ/OmpR two-component regulatory system controls production of two outer membrane porins, OmpF and OmpC, that enable bacterial cells to survive fluctuations in the osmolarity of the growth medium. This pathway is one of several well-characterized two-component systems, with others including the chemotaxis system and the NtrB/C system involved in nitrogen regulation. The OmpR regulon has recently proven to be more complex than it once appeared. Hence, it is important not only in regulating the porin genes ompF and ompC, but it also plays a role at the ssrA/B-spiC locus on Salmonella pathogenicity island-2 (SPI-2) and at the curli fimbrial regulon in Escherichia coli. In addition to those genes, OmpR affects others outside the porin repertoire, regulating loci as diverse as the master flagellar operon flhDC, the Salmonellainduced filament protein SifA, and the fatty acid receptor fadL. OmpR also plays a role in regulating a variety of virulence genes in the pathogens Shigella flexneri, Yersinia enterocolitica, Salmonella typhi, and S. typhimurium. In several systems, ompR mutants are attenuated for virulence, because they are either unable to escape from macrophages, spread cell to cell, or kill epithelial cells.