Regulation of the spvR gene of the Salmonella typhimurium virulence plasmid during exponential-phase growth in intracellular salts medium and at stationary phase in L broth.

The authors previously showed that the SpvR-regulated spvABCD operon of the Salmonella typhimurium virulence plasmid is highly induced during exponential-phase growth by salmonellae intracellularly in mammalian cells and in a medium designed to mimic the intracellular environment of mammalian cells, intracellular salts medium (ISM), as well as at stationary phase in L broth (LB). The most relevant signal(s) for spv gene expression in vivo is not known. To elucidate the means by which salmonellae regulate the spv genes in response to the environment during the disease process, expression of the spvR gene, encoding the positive regulatory protein SpvR, was examined under these same growth conditions by using RNAse-protection analysis. spvR was expressed at a low, basal level during exponential growth in LB but was induced during exponential growth in ISM and during stationary phase in LB, the same conditions that increased expression of the spvABCD operon. Basal expression of spvR during exponential growth in LB was independent of both SpvR and the alternative sigma factor RpoS, whereas maximal induction of spvR was dependent on both SpvR and RpoS. In an RpoS- background, spvR message was decreased in stationary phase, whereas spvR exhibited residual RpoS-independent induction during exponential growth in ISM. Deletion of spvA from the virulence plasmid of S. typhimurium increased expression of spvR during stationary phase in LB, but not during exponential growth in ISM. These results suggest that expression of spvR is controlled by different regulatory factors, depending on the growth conditions encountered by the salmonellae.