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 (DeltappGpp strain), which is defective in ppGpp synthesis, was virtually avirulent in BALB/c mice. Subsequently, the live vaccine potential of the avirulent DeltappGpp Salmonella strain was determined. A single immunization with live DeltappGpp Salmonella efficiently protected mice from challenge with wild-type Salmonella at a dose 10(6)-fold above the LD50 30 days after immunization. Various assays revealed that immunization of mice with the DeltappGpp strain elicited both systemic and mucosal antibody responses, in addition to cell-mediated immunity.
Na
Hee Sam
HS
Genome Research Center for Enteropathogenic Bacteria and Research Institute of Vibrio Infection, South Korea.
Kim
Hyun Ju
HJ
Lee
Hyun-Chul
HC
Hong
Yeongjin
Y
Rhee
Joon Haeng
JH
Choy
Hyon E
HE
D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D044404:Genomic Islands / Q000235:genetics / Q000502:physiology; D006159:Guanosine Tetraphosphate / Q000096:biosynthesis / Q000378:metabolism*; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D012480:Salmonella Infections / Q000276:immunology / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000276:immunology* / Q000378:metabolism
D001428:Bacterial Vaccines; D006159:Guanosine Tetraphosphate