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Pathogen activators of plasminogen
Author(s) -
Verhamme I. M.,
Panizzi P. R.,
Bock P. E.
Publication year - 2015
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12939
Subject(s) - plasmin , zymogen , virulence , streptokinase , pathogen , bacterial adhesin , streptococcus pyogenes , microbiology and biotechnology , chemistry , biology , bacteria , enzyme , biochemistry , genetics , gene , staphylococcus aureus , psychology , psychiatry , myocardial infarction
Summary Group A streptococci ( GAS ) express soluble and surface‐bound virulence factors. Secreted streptokinase ( SK ) allelic variants exhibit varying abilities to activate host plasminogen ( P g), and GAS pathogenicity is associated with P g activation and localization of the resulting plasmin ( P m) on the bacterial surface to promote dissemination. The various mechanisms by which GAS usurp the host proteolytic system are discussed, including the molecular sexuality mechanism of conformational activation of the P g zymogen ( P g*) and subsequent proteolytic activation of substrate P g by the S•KPg* and SK•Pm catalytic complexes. Substantial progress has been made to delineate both processes in a unified mechanism. Pm coats the bacteria by direct and indirect binding pathways involving plasminogen‐binding group A streptococcal M‐like (PAM) protein and host fibrin(ogen). Transgenic mouse models using human P g are being optimized to mimic infections by SK variants in humans and to define in vivo combined mechanisms of these variants and PAM .