title: A Serine-Threonine Kinase (StkP) Regulates Expression of the Pneumococcal Pilus and Modulates Bacterial Adherence to Human Epithelial and Endothelial Cells In Vitro.
abstract: The pneumococcal serine threonine protein kinase (StkP) acts as a global regulator in the pneumococcus. Bacterial mutants deficient in StkP are less virulent in animal models of infection. The gene for this regulator is located adjacent to the gene for its cognate phosphatase in the pneumococcal genome. The phosphatase dephosphorylates proteins phosphorylated by StkP and has been shown to regulate a number of key pneumococcal virulence factors and to modulate adherence to eukaryotic cells. The role of StkP in adherence of pneumococci to human cells has not previously been reported. In this study we show StkP represses the pneumococcal pilus, a virulence factor known to be important for bacterial adhesion. In a serotype 4 strain regulation of the pilus by StkP modulates adherence to human brain microvascular endothelial cells (HBMEC) and human lung epithelial cells. This suggests that the pneumococcal pilus may play a role in adherence during infections such as meningitis and pneumonia. We show that regulation of the pilus occurs at the population level as StkP alters the number of pili-positive cells within a single culture. As far as we are aware this is the first gene identified outside of the pilus islet that regulates the biphasic expression of the pilus. These findings suggest StkPs role in cell division may be linked to regulation of expression of a cell surface adhesin.
authors.affiliation: Institute of Microbiology and Infection, School of Immunity and Infection, University of Birmingham, Birmingham, England, United Kingdom.
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Herbert
authors.affiliation: Institute of Microbiology and Infection, School of Immunity and Infection, University of Birmingham, Birmingham, England, United Kingdom.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Mitchell
authors.affiliation: Institute of Microbiology and Infection, School of Immunity and Infection, University of Birmingham, Birmingham, England, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mitchell
mesh_terms: D001422:Bacterial Adhesion / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000382:microbiology*; D004847:Epithelial Cells / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D017346:Protein Serine-Threonine Kinases