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 monocytog enes, a previously unknown Clp ATPase, unique among the HSP100 proteins bec ause of the presence of a short N-terminal region with a potential zinc fin ger 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 conse nsus ae promoter. clpE is not stimulated by various stresses, but is upregu lated in a clpC mutant. This is the first example of cross-regulation betwe en 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 involv ed in the virulence of this pathogen. A double mutant deficient in both Clp E and ClpC was avirulent in a mouse model and completely eliminated in the liver. Electron microscopy studies did not show any morphological alteratio ns in clpE or clpC mutants. In the clpE-clpC double mutant, however, cell d ivision was affected, indicating that ClpE acts synergistically with ClpC i n cell septation. These results show that the Clp chaperones play a crucial role in both cell division and virulence of L. monocytogenes.