Phenotypic and Transcriptional Characterization of the Meningococcal PhoPQ System, a Magnesium-Sensing Two-Component Regulatory System That Controls Genes Involved in Remodeling the

We previously identified and characterized a two-component regulatory system in the meningococcus with homology to the phoP-phoQ system in salmonella and showed that allele replacement of the NMB0595 regulator gene led to loss of virulence, sensitivity to antimicrobial peptides, perturbed protein expression, and magnesium-sensitive growth. On the basis of these findings we proposed that the system should be designated the meningococcal PhoPQ system. Here we further characterized the NMB0595 mutant and demonstrated that it had increased membrane permeability and was unable to form colonies on solid media with low magnesium concentrations, features that are consistent with disruption of PhoPQ-mediated modifications to the lipooli-gosaccharide structure. We examined the transcriptional profiles of wild-type and NMB0595 mutant strains and found that magnesium-regulated changes in gene expression are completely abrogated in the mutant, indicating that, similar to the salmonella PhoPQ system, the meningococcal PhoPQ system is regulated by magnesium. Transcriptional profiling of the mutant indicated that, also similar to the salmonella PhoPQ system, the meningococcal system is involved in control of virulence and remodeling of the bacterial cell surface in response to the host environment. The results are consistent with the hypothesis that the PhoP homologue plays a role in the meningococcus similar to the role played by PhoP in salmonella. Elucidating the role that the PhoPQ system and PhoPQ-regulated genes play in the response of the meningococcus to the hos