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Infect. Immun. doi:10.1128/IAI.01716-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Modulation of adherence, invasion, and TNF- secretion during the early stages of infection by Streptococcus pneumoniae ClpL

College of Pharmacy, Sungkyunkwan University, Suwon, 440-746, South Korea; School of Molecular and Biomedical Science, The University of Adelaide, 5005, Australia

^* To whom correspondence should be addressed. Email: dkrhee{at}skku.edu.

	Abstract

Heat shock proteins (HSPs) play a pivotal role as chaperones in the folding of native and denatured proteins, and can benefit pathogens in penetrating host defenses. However, the underlying mechanism(s) of modulation of virulence by HSPs has not been fully determined. In this study, the role of the chaperone ClpL in the pathogenicity of Streptococcus pneumoniae was assessed. A clpL mutant adhered to and invaded nasopharyngeal or lung cells much more efficiently than the wild type in vitro as well as in vivo, although it produced the same amount of capsular polysaccharide. However, secretion of TNF- from macrophages infected with the clpL mutant was significantly lower than that elicited by the wild type during the early stages of infection. Interestingly, treatment of human lung epithelial carcinoma A549 and murine macrophage RAW264.7 cell lines with cytochalasin D, an inhibitor of actin polymerization, increased adherence of the mutant to the host cells. In contrast, cytochalasin D treatment of RAW264.7 cells decreased TNF- secretion after infection with either the wild type or the mutant. However, pretreatment of cell lines with the actin polymerization activator, jasplakinolide, reversed these phenotypes. These findings indicate, for the first time, that the ClpL chaperone represses adherence of S. pneumoniae to host cells and induces secretion of TNF- via a mechanism dependent upon actin polymerization during the initial infection stage.