ClpC ATPase is required for cell adhesion and invasion of Listeria monocytogenes

We studied the role of two members of the 100-kDa heat shock protein family , the ClpC and ClpE ATPases, in cell adhesion and invasion of the intracell ular pathogen Listeria monocytogenes. During the early phase of infection, a clpC mutant failed to disseminate to hepatocytes in the livers of infecte d mice whereas the invasive capacity of a clpE mutant remained unchanged. T his was confirmed by a confocal microscopy study on infected cultured hepat ocyte and epithelial cell lines, showing a strong reduction of cell invasio n only by the clpC mutant. Western blot analysis with specific antisera sho wed that the absence of ClpC, but not that of ClpE, reduced expression of t he virulence factors InlA, InlB, and ActA. ClpC-dependent modulation of the se factors occurs at the transcriptional level with a reduction in the tran scription of inlA, inlB, and actA in the clpC mutant, in contrast to the cl pE mutant. This work provides the first evidence that, in addition to promo ting escape from the phagosomes, ClpC is required for adhesion and invasion and modulates the expression of InlA, InlB, and ActA, further supporting t he major role of the Clp chaperones in the virulence of intracellular patho gens.