Chaperones and Proteases Regulate Two-Component System Signaling in the Bacterial Pathogen Bacillus anthracis

Abstract:

All bacteria experience cues from their internal or external environment that affect their behavior. One way that bacteria monitor their environment is through the use of two-component sensor systems (TCS). A two-component system consists of a histidine kinase sensor in the cell membrane which phosphorylates a cytoplasmic response regulator that alters transcription. In many cases, the regulatory events controlling activity or abundance of response regulators and histidine kinases are not fully characterized. Here, we present results from a genetic screen aimed at identifying regulators of TCS in the pathogen Bacillus anthracis. We find that the stress-sensing TCS HitR-HitS is regulated by the activity of the chaperone proteases ClpX and DnaJ. DnaJ regulates the levels of HitR and HitS to facilitate signal transduction, while ClpX specifically regulates HitS levels. Together these results reveal that the protein homeostasis regulators DnaJ and ClpX function to maintain signal transduction activities through TCS regulation.