Infection-relevant conditions dictate differential versus coordinate expression of chaperones and cochaperones.

Molecular chaperones are critical for protein homeostasis. In bacteria, chaperone trigger factor (TF) folds proteins co-translationally, and chaperone DnaK requires a J-domain cochaperone and nucleotide exchange factor GrpE to fold proteins largely post-translationally. However, when the pathogen serovar Typhimurium faces the infection-relevant condition of cytoplasmic Mg starvation, DnaK reduces protein synthesis independently. This raises the possibility that bacteria differentially express chaperones and cochaperones. We now report that . Typhimurium responds to cytoplasmic Mg starvation by increasing mRNA amounts of while decreasing those of the TF-encoding gene and J-domain cochaperone genes and . This differential strategy requires the master regulator of Mg homeostasis and virulence PhoP, which increases mRNA amounts by lowering the ATP concentration, thereby hindering proteolysis of the alternative sigma factor RpoH responsible for transcription. We also establish that DnaK exerts negative feedback on the RpoH protein and RpoH-dependent transcripts independently of J-domain cochaperones. Thus, bacteria express chaperones and cochaperones coordinately or differentially depending on the specific stress perturbing protein homeostasis.IMPORTANCEMolecular chaperones typically require cochaperones to fold proteins and to prevent protein aggregation, and the corresponding genes are thus coordinately expressed. We have now identified an infection-relevant stress condition in which the genes specifying chaperone DnaK and cochaperone DnaJ are differentially expressed despite belonging to the same operon. This differential strategy requires the master regulator of Mg homeostasis and virulence in the pathogen serovar Typhimurium. Moreover, it likely reflects that requires , but not J-domain cochaperone-encoding genes, for survival against cytoplasmic Mg starvation and expresses genes only when needed. Thus, the specific condition impacting protein homeostasis determines the coordinate versus differential expression of molecular chaperones and cochaperones.