Immune response induced by Salmonella typhimurium defective in ppGpp synthesis

Systemic infection by Salmonella typhimurium requires coordinated expression of virulence genes found primarily in Salmonella Pathogenecity Islands (SPIs). We have previously reported that the intracellular signal that induces these virulence genes is a stringent signal molecule, ppGpp [Song et al. J Biol Chem 2003;279:34183]. In this study, we found that relA and spoT double mutant Salmonella (ΔppGpp strain), which is defective in ppGpp synthesis, was virtually avirulent in BALB/c mice. Subsequently, the live vaccine potential of the avirulent ΔppGpp Salmonella strain was determined. A single immunization with live ΔppGpp Salmonella efficiently protected mice from challenge with wild-type Salmonella at a dose 106-fold above the LD50 30 days after immunization. Various assays revealed that immunization of mice with the ΔppGpp strain elicited both systemic and mucosal antibody responses, in addition to cell-mediated immunity.