Altered Transcriptome of the B. melitensis Vaccine Candidate 16MΔvjbR, Implications for Development of Genetically Marked Live Vaccine.

ABSTRACT

The VjbR protein induced antibody responses in both human and animal brucellosis, and the vjbR mutant 16MΔvjbR is an ideal vaccine candidate because of the feasibility of using the VjbR as diagnostic antigen. To further characterize this vaccine candidate and provide information for vaccine development, in the present study, a whole genome DNA microarray of 16M were used to compare the transcriptome of the vjbR mutant to that of the wild type strains. A total of 126 genes were greatly differentially expressed in the vjbR mutant. A great proportion of virB and flagellar genes were differentially expressed in the vjbR mutant, implying that the vjbR regulate expression of virulence genes by sensing intracellular environments. Interestingly, the virB genes are regulated by the vjbR in independent manners as shown by their different fold changes and transcription abundances. A number of genes involved in translation, stress response, amino acid transport and metabolism, cell wall/membrane biogenesis, energy production and conversion, translation were differentially expressed. The vjbR mutant showed increased sensitivity to stresses of nutrition limitation, oxidative stress and acidification, and decreased survival in macrophage and mice, being consistent with its transcription profiles. These results indicated that the quorum sensing regulator vjbR could sense intracellular environments and response to them by regulate expression of virulence genes and other intracellular survival related genes, and therefore contribute to Brucella survival in host cells. This also provided direct evidence for the rational vaccine design by using antigenic global regulator for future development of genetically marked vaccine for brucellosis.