title: The interaction between bacterial enolase and plasminogen promotes adherence of Streptococcus pneumoniae to epithelial and endothelial cells.
abstract: Binding and conversion of the plasma protein plasminogen is an important pathogenesis mechanism of the human pathogen Streptococcus pneumoniae. Once converted into plasmin, the proteolytic activity of this major fibrinolysis component promotes degradation of extracellular matrix and the dissolution of fibrin clots. Here, we present the exploitation of plasminogen-binding as a further pivotal strategy of pneumococci facilitating adherence to eukaryotic cells. Flow cytometric measurements demonstrated the immobilization of plasminogen on host cell surfaces of human alveolar type II pneumocytes (A549), nasopharyngeal epithelium (Detroit 562) and brain-derived endothelial cells (HBMEC). These host-derived cells were employed in cell culture infection analyses followed by confocal microscopy to monitor the plasminogen-mediated adherence. Results of these studies revealed that host cell-bound plasminogen promotes pneumococcal adherence to human epithelial and endothelial cells in dose-dependent manner, whereas pneumococcal internalization was not enhanced. As an opposed effect pneumococcal-bound plasminogen reduced attachment to the epithelial and endothelial cells, and increased the interaction with neutrophil granulocytes. Moreover, the surface-displayed enolase, which serves as major pneumococcal plasminogen receptor, was identified as a key factor for plasminogen-mediated bacterial attachment in infection analyses with S. pneumoniae enolase mutants.
authors.affiliation: Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians University, 80336 Munich, Germany. Electronic address: simone.bergmann@tu-bs.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Bergmann
authors.forename: Hanne
authors.initials: H
authors.lastname: Schoenen
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
mesh_terms: D001422:Bacterial Adhesion; D002460:Cell Line; D004252:DNA Mutational Analysis; D042783:Endothelial Cells / Q000382:microbiology*; D004847:Epithelial Cells / Q000382:microbiology*; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D006801:Humans; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000235:genetics / Q000502:physiology
chemical_list: D010958:Plasminogen; D010751:Phosphopyruvate Hydratase
keywords: Cell adherence; Enolase; Plasminogen; Streptococcus pneumoniae