biostudies-literatureLy DNIAID NIH HHS240-50https://www.ebi.ac.uk/biostudies/studies/S-EPMC6741502biostudies-literatureUnknown6(2)The globally significant human pathogen group A Streptococcus (GAS) sequesters the host protease plasmin to the cell surface during invasive disease initiation. Recent evidence has shown that localized plasmin activity prevents opsonization of several bacterial species by key components of the innate immune system in vitro. Here we demonstrate that plasmin at the GAS cell surface resulted in degradation of complement factor C3b, and that plasminogen acquisition is associated with a decrease in C3b opsonization and neutrophil-mediated killing in vitro. Furthermore, the ability to acquire cell surface plasmin(ogen) correlates directly with a decrease in C3b opsonization, neutrophil phagocytosis, and increased bacterial survival in a humanized plasminogen mouse model of infection. These findings demonstrate that localized plasmin(ogen) plays an important role in facilitating GAS escape from the host innate immune response and increases bacterial virulence in the early stages of infection.Journal of innate immunityPlasmin(ogen) acquisition by group A Streptococcus protects against C3b-mediated neutrophil killing.PMC6741502R01 AI077780McArthur JDMonteleone MMWalker MJDonald CAWest NPSanderson-Smith MLTaylor JMLy DTsatsaronis JASkora ASRanson MMaddocks TNizet VfalsePlasmin(ogen) acquisition by group A Streptococcus protects against C3b-mediated neutrophil killing.The globally significant human pathogen group A Streptococcus (GAS) sequesters the host protease plasmin to the cell surface during invasive disease initiation. Recent evidence has shown that localized plasmin activity prevents opsonization of several bacterial species by key components of the innate immune system in vitro. Here we demonstrate that plasmin at the GAS cell surface resulted in degradation of complement factor C3b, and that plasminogen acquisition is associated with a decrease in C3b opsonization and neutrophil-mediated killing in vitro. Furthermore, the ability to acquire cell surface plasmin(ogen) correlates directly with a decrease in C3b opsonization, neutrophil phagocytosis, and increased bacterial survival in a humanized plasminogen mouse model of infection. These findings demonstrate that localized plasmin(ogen) plays an important role in facilitating GAS escape from the host innate immune response and increases bacterial virulence in the early stages of infection.2014-01-01T00:00:00Z20142021-02-21T09:09:45Z2020-05-22T07:25:53ZS-EPMC67415022396988710.1159/000353754