temperature- and growth phase-dependent regulation of the global virulence regulator RovA from Yersinia pseudotuberculosisThe

Temperature is one of the most crucial signals sensed by pathogenic bacteria to adapt their gene expression program to changing environmental conditions inside and outside the host organism. In Yersinia pseudotuberculosis expression of early virulence genes is regulated by the global transcriptional regulator RovA. rovA expression is regulated by temperature and growth phase. In this work it was demonstrated that RovA acts as an intrinsic protein thermometer that controls its DNA-binding ability by temperature induced structural alterations. In addition, thermo-induced unfolding and, accordingly, reduced DNA binding under non-inducing conditions was found to increase the susceptibility of the protein to degradation by the Lon and ClpP proteases. Furthermore, a secreted factor is responsible for growth phase-dependent regulation of RovA synthesis. This factor, similar to the aromatic compound salicylate, prevents RovA degradation in stationary growth phase. The affinity for the ligand is depending on the hydroxyl group position on the aromatic ring. Production of the RovA-stabilizing factor occurs under nutrient rich conditions in stationary growth phase. Moreover, it was shown that the rovA gene is heterogeneously expressed. Two distinct populations could be observed at 32°C during exponential growth. Based on the known rovA regulatory mechanisms it is suggested that heterogeneous rovA expression originates from bistability. Taken together, the temperature and growth phase dependent RovA regulation and the resulting heterogeneous gene expression both constitute a new example of how a microbial pathogen is able to rapidly adjust its virulence gene expression program to changing environmental conditions during the course of an infection.