The ClpP serine protease is essential for the intracellular parasitism and virulence of Listeria monocytogenes.
We identified the stress-induced ClpP of Listeria monocytogenes and demonstrated 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 prokaryotes and eukaryotes. A clpP-deleted mutant enabled us to demonstrate that ClpP is involved in proteolysis and is required for growth under stress conditions. Intramacrophage survival of this mutant was strongly restricted, thus resulting in loss of virulence for the mouse. The activity of listeriolysin O, a major virulence factor implicated in bacterial escape from phagosomes of macrophages, was much reduced in the clpP mutant under stress conditions. Direct evidence for the role of ClpP in the intracellular parasitism was obtained by showing that virulence and haemolytic activity were fully 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.
Gaillot
O
O
INSERM U411, Centre Hospitalo-Universitaire Necker-Enfants Malades, 156, rue de Vaugirard, 75730 PARIS Cedex 15, France.
Pellegrini
E
E
Bregenholt
S
S
Nair
S
S
Berche
P
P
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins; D002455:Cell Division; D049071:Endopeptidase Clp; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006460:Hemolysin Proteins; D008089:Listeria monocytogenes / Q000201:enzymology* / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D013696:Temperature; D014774:Virulence
D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases; C038705:hlyA protein, Listeria monocytogenes