ABSTRACT Streptococcus pyogenes (group A streptococci; GAS) show specificity for a wide range of human tissue sites. Infection with GAS can result in highly invasive diseases such as bacteraemia and necrotizing fasciitis, while serious sequelae, such as rheumatic fever may also result from infection. A resurgence of severe invasive GAS disease occurred in industrialised countries in the mid 1980’s. However, the level of exposure to GAS and the incidence of GAS infection and post-streptococcal disease is far greater in many developing countries, where the epidemiology of endemic isolates appears to differ from that of isolates in industrialised countries. Evidence is accumulating which implicates the plasminogen activation system (PAS) in a variety of streptococcal diseases. Apart from the secreted protein streptokinase, a known activator of plasminogen, four distinct GAS plasminogen binding proteins have been described in the literature. Isolates associated with invasive infection have recently been demonstrated to bind more plasminogen than isolates from uncomplicated infections; subversion of the host PAS by GAS is also correlated with invasion in animal models. Furthermore, certain GAS gene products that interact with the PAS appear to play a role in host tissue tropism of streptococcal disease. Despite major advances in our understanding of plasminogen activation by GAS, much remains to be clarified. This review outlines the current understanding of the interactions between GAS and this host proteolytic system, as well as discussing future research directions regarding the role of plasminogen in GAS pathogenesis.
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