Bimodal Expression of the Typhimurium Operon.

The well-studied operon of is important for causing full virulence in mice and both the regulation and function of the Spv proteins have been characterized extensively over the past several decades. Using quantitative single-cell fluorescence microscopy, we demonstrate the regulon to display a bimodal expression pattern that originates in the bimodal expression of the SpvR activator. The expression pattern is influenced by growth conditions and the specific strain used, but does not require -specific virulence regulators. By monitoring real-time promoter kinetics, we reveal that SpvA has the ability to impart negative feedback on expression without affecting expression. Together, our data suggest that the SpvA protein counteracts the positive feedback loop imposed by SpvR, and could thus be responsible for dampening expression and coordinating virulence protein production in time. The results presented here yield new insights in the intriguing regulation of the operon and adds this operon to the growing list of virulence factors exhibiting marked expression heterogeneity in .