The ATP-dependent caseinolytic proteases (Clp) play a fundamental role in stress tolerance and virulence in many pathogenic bacteria. Although ClpE of Streptococcus pneumoniae is required for growth at high temperatures, little is known about the role of ClpE in pathogenesis. In this study, we observed that the virulence of the clpE mutant of S. pneumoniae strain D39 was strongly reduced in a mouse intraperitoneal infection model. The clpE mutant also showed substantially reduced adherence to the human lung epithelial carcinoma A549 cell line and human umbilical-vein-derived endothelial cells. The underlying mechanism of virulence attenuation induced by the mutation of clpE was further investigated with real-time RT-PCR and 2-dimensional protein gel analysis. The results indicate that ClpE affects pneumococcal pathogenesis by modulating the expression of some important virulence determinants and metabolism-related factors in S. pneumoniae.
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