The ClpP serine protease is essential for the intracellular parasitism andvirulence of Listeria monocytogenes

We identified the stress-induced ClpP of Listeria monocytogenes and demonst rated its crucial role in intracellular survival of this pathogen. ClpP is a 21.6 kDa protein belonging to a family of proteases highly conserved in p rokaryotes and eukaryotes. A clpP-deleted mutant enabled us to demonstrate that ClpP is involved in proteolysis and is required for growth under stres s conditions. Intramacrophage survival of this mutant was strongly restrict ed, thus resulting in loss of virulence for the mouse. The activity of list eriolysin O, a major virulence factor implicated in bacterial escape from p hagosomes of macrophages, was much reduced in the clpP mutant under stress conditions. Direct evidence for the role of ClpP in the intracellular paras itism was obtained by showing that virulence and haemolytic activity were f ully restored by complementation of the mutant. These results suggest that ClpP is involved in the rapid adaptive response of intracellular pathogens during the infectious process.