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.