ClpE, a novel member of the HSP100 family, is involved in cell division and virulence of Listeria monocytogenes.
We identified, in the facultative intracellular pathogen Listeria monocytogenes, a previously unknown Clp ATPase, unique among the HSP100 proteins because of the presence of a short N-terminal region with a potential zinc finger motif. This protein of 726 amino acids is highly homologous to ClpE of Bacillus subtilis, and is a member of a new subfamily of HSP100/Clp ATPases. The clpE gene is transcribed as a monocistronic mRNA from a typical consensus sigma A promoter. clpE is not stimulated by various stresses, but is upregulated in a clpC mutant. This is the first example of cross-regulation between Clp ATPases. By constructing a clpE mutant of L. monocytogenes, we found that ClpE is required for prolonged survival at 42 degrees C and is involved in the virulence of this pathogen. A double mutant deficient in both ClpE and ClpC was avirulent in a mouse model and completely eliminated in the liver. Electron microscopy studies did not show any morphological alterations in clpE or clpC mutants. In the clpE-clpC double mutant, however, cell division was affected, indicating that ClpE acts synergistically with ClpC in cell septation. These results show that the Clp chaperones play a crucial role in both cell division and virulence of L. monocytogenes.
Nair
S
S
Inserm U411, Faculté de Médecine Necker, Paris, France. snair@pasteur.fr
Frehel
C
C
Nguyen
L
L
Escuyer
V
V
Berche
P
P
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D002455:Cell Division; D003001:Cloning, Molecular; D004269:DNA, Bacterial; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000502:physiology; D008089:Listeria monocytogenes / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014774:Virulence