Interaction between Group A Streptococci and the Plasmin(ogen) System Promotes Virulence in a Mouse Skin Infection Model

Abstract

Group A streptococci are capable of acquiring a surface-associated, unregulatable plasmin-like enzymatic activity when incubated in human plasma. The effect of this enzymatic activity on virulence of group A isolate CS101 was examined in a mouse skin infection model. Initial studies demonstrated enhanced virulence for bacteria preincubated in human plasma but not in plasminogen-depleted plasma. A direct correlation between surface-associated enzymatic activity and virulence was not observed; however, an association between virulence and the assembly of a surface-associated plasminogen activator that could activate mouse plasminogen was noted. This activity enhanced virulence in wild type but not in plg-/- plasminogen-deficient mice. These results support the hypothesis that acquisition of a surface-associated plasmin(ogen)-dependent enzymatic activity can contribute to the virulence of group A streptococcal invasive infections.

Molecular cloning and characterization of two Helicobacter pylori genes coding for plasminogen-binding proteins

“…7). The role of Pg in bacterial pathogenesis has been confirmed in animal studies with group A streptococci (13), Y. pestis (16), B. burgdorferi (14), and B. crocidurae (15).…”

“…For group A streptococci (13), B. burgdorferi (14), Borrelia crocidurae (15), and Yersinia pestis (16), Pg has been demonstrated to be important for virulence in vivo. It is believed that tissue penetration and dissemination are facilitated by the acquisition of Pg on the bacterial surface and subsequent activation of this surface-associated Pg by a host-derived Pg activator such as tissue Pg activator (tPA) or urokinase Pg activator.…”

Plasminogen interaction with Trypanosoma cruzi

“…Other plasminogen-binding pathogens may be capable of using host plasminogen activator (Lähteenmäki et al 2001). In the case of Y. pestis, Borrelia burgdorferi, and group A Streptococci, the interaction with plasminogen has been demonstrated to be implicated in the invasiveness within the host (Gebbia et al 1999, Li et al 1999, Goguen et al 2000. The suggested functions for plasmin in pathogenic infection include extracellular matrix protein degradation, fi-brin degradation, release of peptides for nutrition, and metalloprotease activation.…”

Host–Pathogen Interactions in Tuberculosis

“…Among bacteria are Borrelia burgdorferi (Fuchs et al, 1994), Escherichia coli (Kukkonen et al, 1998;Lähteenmäki et al, 1993;Parkkinen et al, 1991), Salmonella typhimurium (Korhonen et al, 1997;Kukkonen et al, 1998;Lähteenmäki et al, 1995), Neisseria meningitidis (Ullberg et al, 1992) and Haemophilus influenzae (Sjostrom et al, 1997) and group A, B and C of streptococci (Lähteenmäki et al, 2001b;Coleman & Benach, 1999). In contrast to the high number of PlgR described in bacteria, only a few PAs has been identified, the plasminogen activator in Yersinia pestis (Pla) (Perry & Fetherston, 1997;Sodeinde et al, 1992), the staphylokinase (SK) of Staphylococcus aureus (Esmon & Mather, 1998;Lijnen et al, 1994) and the streptokinase (SAK) of Streptococcus pyogenes (Li et al, 1999;Sun et al, 2004).…”