Abstract Number: LPB0113
Meeting: ISTH 2021 Congress
Background: Human plasmin (hPm) proteolytic activity is utilized by various pathogenic bacteria, such as Group A Streptococcus (GAS), to increase their dissemination and pathogenicity. GAS is a human-selective Gram-positive coccus bacterium that utilizes the function of hPm through the expression of surface human plasminogen (hPg) receptors. Once hPg is recruited to the cell surface, it is converted into active hPm. There are at least three hPg receptors on the GAS cell surface with different binding strengths to hPg. Plasminogen-binding Group A Streptococcal M-protein (PAM) is typically found on skin-tropic Pattern D GAS strains, such as AP53. PAM binds hPg with a very high affinity (Kd ~1 nM) and is able to stimulate hPg activation in the presence of GAS-secreted streptokinase (SK) and hPg activators such as urokinase (uPA). Unlike PAM, another hPg receptor, streptococcal surface enolase (SEN), is found on the surface of most GAS strains and its importance to hPg acquisition in skin-tropic GAS strain is not known, especially when PAM is also present.
Aims: This study presents the results of an investigation on the contribution of SEN in hPg binding and activation.
Methods: Analytical ultracentrifugation, isothermal titration calorimetry, and flow cytometry were used in this study.
The data generated showed that the 45 kDa monomer unit of recombinant SEN oligomerizes to form a highly stable octamer in solution. The octameric SEN forms a complex with hPg, characterized by a Kd of ~100 nM. Although SEN tightly binds hPg, it does not stimulate hPg activation by SK or uPA. Whole GAS cell studies showed that the surface expression of SEN is diminished upon targeted deletion of the PAM gene. hPg binding to AP53 cells emphasizes a lower affinity of SEN for hPg compared to PAM.
Conclusions: This study strongly suggests that SEN plays a secondary role as hPg receptor in skin-tropic GAS strains.
To cite this abstract in AMA style:Tjia-Fleck S, Ayinuola Y, Liang Z, Ploplis V, Castellino F. Streptococcal Surface Enolase (SEN) Is Overshadowed by Plasminogen-binding Group A Streptococcal M-protein (PAM) for Human Plasminogen Acquisition and Activation [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/streptococcal-surface-enolase-sen-is-overshadowed-by-plasminogen-binding-group-a-streptococcal-m-protein-pam-for-human-plasminogen-acquisition-and-activation/. Accessed November 30, 2021.
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