ClpP is involved in the stress response and degradation of misfolded proteins in Salmonella enterica serovar Typhimurium.

Components of the ATP-dependent Clp protease complex are found in a wide range of prokaryotic cells and they are often expressed as part of the cellular stress response. To investigate the physiological role of the proteolytic subunit, ClpP, in Salmonella enterica serovar Typhimurium (S. typhimurium) an in-frame deletion of the clpP gene was constructed. Growth experiments revealed that clpP is important for the ability of S. typhimurium to grow under various stressful conditions, such as low pH, elevated temperature and high salt concentrations. Since the stationary-phase sigma factor, RpoS, is a target of the Clp proteolytic complex, the effect of the clpP deletion in the absence of RpoS was examined; it was observed that growth of the S. typhimurium clpP mutant is affected in both an RpoS-dependent and an RpoS-independent manner. Analysis of the degradation of abnormal puromycyl-containing polypeptides showed that ClpP participates in the proteolysis of such proteins in S. typhimurium. These findings prompted an investigation of the growth of an Escherichia coli clpP mutant under various stress conditions. The growth of this E. coli mutant was affected by heat, salt and low pH, although not to the same extent as observed for the S. typhimurium clpP mutant. The results of this study indicate that the S. typhimurium clpP mutant is generally more sensitive to environmental stress than the E. coli clpP mutant and it is proposed that this is due to a reduced ability to degrade misfolded proteins generated under these conditions.