This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.01716-06v1 75/6/2996    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tu, L. N. Articles by Rhee, D.-K. Search for Related Content PubMed PubMed Citation Articles by Tu, L. N. Articles by Rhee, D.-K.

Modulation of Adherence, Invasion, and Tumor Necrosis Factor Alpha Secretion during the Early Stages of Infection by Streptococcus pneumoniae ClpL

Le Nhat Tu,^1, Hye-Yoon Jeong,^1, Hyog-Young Kwon,¹ Abiodun D. Ogunniyi,² James C. Paton,² Suhk-Neung Pyo,¹ and Dong-Kwon Rhee^1*

College of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea,¹ School of Molecular and Biomedical Science, The University of Adelaide, Adelaide 5005, Australia²

Received 26 October 2006/ Returned for modification 19 December 2006/ Accepted 21 March 2007

Heat shock proteins (HSPs) play a pivotal role as chaperones in the folding of native and denatured proteins and can help pathogens penetrate 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 adhered to and invaded these cells in vitro, as well as in vivo, although it produced the same amount of capsular polysaccharide. However, the level of secretion of tumor necrosis factor alpha (TNF-) from macrophages infected with the clpL mutant was significantly lower than the level of secretion elicited by the wild type during the early stages of infection. Interestingly, treatment of the human lung epithelial carcinoma A549 and murine macrophage RAW 264.7 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 RAW 264.7 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.

Published ahead of print on 2 April 2007.

Editor: J. N. Weiser

L.N.T. and H.-Y.J. contributed equally to this work.