title: Modulation of adherence, invasion, and tumor necrosis factor alpha secretion during the early stages of infection by Streptococcus pneumoniae ClpL.
abstract: 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-alpha) 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-alpha 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-alpha via a mechanism dependent upon actin polymerization during the initial infection stage.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea. dkrhee@skku.edu
authors.forename: Le Nhat
authors.initials: le N
authors.lastname: Tu
authors.forename: Hye-Yoon
authors.initials: HY
authors.lastname: Jeong
authors.forename: Hyog-Young
authors.initials: HY
authors.lastname: Kwon
authors.forename: Abiodun D
authors.initials: AD
authors.lastname: Ogunniyi
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
authors.forename: Suhk-Neung
authors.initials: SN
authors.lastname: Pyo
authors.forename: Dong-Kwon
authors.initials: DK
authors.lastname: Rhee
mesh_terms: D001422:Bacterial Adhesion; D049071:Endopeptidase Clp / Q000235:genetics; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D011008:Pneumococcal Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013296:Streptococcus pneumoniae; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha; D049071:Endopeptidase Clp