The response regulator PhoP is important for survival under conditions of macrophage-induced stress and virulence in Yersinia pestis

The two-component regulatory system PhoPQ has been identified in many bacte rial species. However, the role of PhoPQ in regulating virulence gene expre ssion in pathogenic bacteria has been characterized only in Salmonella spec ies. We have identified, cloned, and sequenced PhoP orthologues from Yersin ia pestis, Yersinia pseudotuberculosis and Yersinia enterocolitica. To inve stigate the role of PhoP in the pathogenicity of Y. pestis, an isogenic pho P mutant was constructed by using a reverse-genetics PCR-based strategy, Th e protein profiles of the wild-type and phoP mutant strains, grown at eithe r 28 or 37 degrees C, revealed more than 20 differences, indicating that Ph oP has pleiotrophic effects on gene expression in I: pestis, The mutant sho wed a reduced ability to survive in J774 macrophage cell cultures and under conditions of low pH and oxidative stress in vitro, The mean lethal dose o f the phoP mutant in mice was increased 75-fold in comparison with that of the wild-type strain, indicating that the PhoPQ system plays a key role in regulating the virulence of Y. pestis.