Analysis of an orphan two-component system response regulator (VarA) that controls the expression of Rhodococcus equi virulence gene (VapA)
Azuonye, Ijeoma Adaoha
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Virulence of the intracellular pathogen of foals and AIDS patients, Rhodococcus equi, requires the plasmid encoded virulence determinant VapA (virulence associated protein A). The role of a putative orphan two-component transcriptional response regulator, VarA (virulence associated regulator), in vapA expression was examined. A varA deletion mutant was shown to produce reduced amounts of VapA protein. In a murine R. equi infection model, the varA regulator mutant was attenuated to the same extent as a vapA mutant. The direct and specific binding of VarA to the vapA promoter region was established. Bioinformatic analysis of the R. equi genome yielded 20 putative histidine kinases. Of these, two were found to interact with VarA in yeast-two-hybrid (Y2H) direct mating experiments. A traditional Y2H library screen revealed a novel type of interaction between VarA and a serine-threonine kinase-like molecule. If confirmed outside of the yeast system, these interactions purport of a highly complex virulence regulatory network.