Interaction of streptococcal plasminogen binding proteins with the host fibrinolytic system

Abstract

The ability to take advantage of plasminogen and its activated form plasmin is a common mechanism used by commensal as well as pathogenic bacteria in interaction with their respective host. Hence, a huge variety of plasminogen binding proteins and activation mechanisms exist. This review solely focuses on the genus Streptococcus and, in particular, on the so-called non-activating plasminogen binding proteins. Based on structural and functional differences, as well as on their mode of surface linkaging, three groups can be assigned: M-(like) proteins, surface displayed cytoplasmatic proteins with enzymatic activities ("moonlighting proteins") and other surface proteins. Here, the plasminogen binding sites and the interaction mechanisms are compared. Recent findings on the functional consequences of these interactions on tissue degradation and immune evasion are summarized.

Keywords: M-protein; SCM; Streptococcus; enolase; phagocytosis; plasminogen; transmigration.

Figure 1

Schematic model of a window section through a microvessel, presenting different functional mechanisms induced by interaction of streptococci with plasminogen and plasmin. In the upper left site, binding of tPA to the pneumococcal PGK and binding of PLG to surface displayed moonlighting proteins is shown. Subsequent recruitment of PLG and a plasminogen activator leads to generation of plasmin activity on the bacterial surface. Similarly, PLG binding to streptococcal M-and M-like-proteins is followed by activation to plasmin via host-derived activators (upper right). Plasminogen binding also protects against phagocytic killing by granulocytes and macrophages and promotes adherence to endothelial cells (bottom right). Dissolution of fibrin thrombi by surface-bound plasmin-activity facilitating streptococcal transmigration is depicted on the lower left. Proteolytic degradation of extracellular matrix by recruited plasmin activity promotes bacterial-cell contact and pericellular transmigration as illustrated at the bottom center.