Disease relevance of spvR

• In vivo analysis of the interactions of the LysR-like regulator SpvR with the operator sequences of the spvA and spvR virulence genes of Salmonella typhimurium [1].
• It was shown that expression of a transcriptional spvAB'-lacZ fusion could be restored in E. coli and Salmonella katF mutants when spvR was expressed in trans from an exogenous promoter [2].

High impact information on spvR

• These are the integration host factor (IHF), which binds to DNA sequences upstream of the spvR regulatory gene, and the leucine-responsive regulatory protein (Lrp), which binds to sequences upstream of the spvABCD operon [3].
• The spvR gene was found to possess an operator site that resembled closely the distal SpvR binding site of the spvA operator [1].
• However, despite the improved interaction with the transcriptional activator, the altered regulatory region was poorer at promoting spvR gene transcription than the wild type [1].
• The interaction of the Salmonella typhimurium virulence gene regulator, SpvR, with its operator sites upstream of the spvA and spvR genes was analysed in vivo by dimethyl sulphate (DMS) footprinting and site-directed mutagenesis [1].
• Although virulence plasmids differ between serovars, all contain a highly conserved 8-kb region containing the spv locus that encodes the spvR regulatory gene and four structural spvABCD genes [4].

Biological context of spvR

• When the nucleotide sequence of the spvR operator was altered at two nucleotides so that it corresponded more precisely to that of the distal site of the spvA operator, strong SpvR-DNA interactions were detected, with nucleotides in the region -31 to -67 being protected from DMS methylation in vivo [1].
• These data are consistent with spvR being poorly transcribed from the single-copy virulence plasmid in S. typhimurium LT2 and with a suppression of this defect via inactivation of the cAMP-CRP system [5].
• Using these mutants, we demonstrated by mRNA and gene fusion analyses that sigma S, in conjunction with SpvR, controls the transcription of the regulatory gene spvR [2].
• The amino acid sequence of this open reading frame had significant homology to members of the LysR family of positive regulatory proteins; thus, the gene was named spvR (salmonella plasmid virulence) [6].
• The sigma S-regulated gene spvR of Salmonella typhimurium encodes an autoregulatory protein required for transcriptional activation of the virulence operon spvABCD [7].

Other interactions of spvR

• Enhanced spvB transcription was not seen in crp or cya mutants in the absence of a functional spvR positive regulatory gene, showing that the cAMP-CRP system acted on spvB expression either in conjunction with or via SpvR [5].
• The level of spvR transcription originating at spvRp1 was 20-fold higher in the wild-type strain than in the rpoS mutant [8].
• A transposon insertion mutation in hns, the gene encoding H-NS, resulted in enhanced transcription of the spvR regulatory gene and the spvB structural gene in stationary phase cultures [9].

References