A Salmonella peptidase that is important for macrophage survival

Salmonellae cause a variety of diseases in humans and animals. The virulence properties of Salmonella are controlled, in part, by a two-component regulatory system designated PhoP/PhoQ. PhoP/PhoQ governs the expression of several genes in response to host signals. We studied a PhoP-activated gene, pcgL, encoding a gene product with amino acid similarity to a D-Ala-D-Ala dipeptidase of Enterococcus faecium. The pcgL gene is responsible for a D-Ala-D-Ala hydrolytic activity of Salmonella enterica grown under conditions that promote expression of PhoP-activated genes. This activity was absent from strains harboring mutations in either the phoP or pcgL genes. We demonstrated that the PcgL protein is necessary for optimal replication in macrophages. Since Salmonella changes its peptidoglycan structure when grown within host cells and the substrate for PcgL (D-alanyl- D-alanine) is produced for synthesis of the peptidoglycan in Gram- negative bacteria, we hypothesize that the PcgL protein may be responsible for the changes in peptidoglycan structure, that occur during infection. Peptidoglycan- derived products of different bacteria have been implicated in the modulation of early host responses. We propose to study the virulence role of the PcgL protein by; (1) determining the cytokine production of macrophages and during murine infection, (2) characterizing the biochemical properties of the PcgL protein, and (3) continuing the molecular characterization of the region harboring the pcgL gene.