M protein‐mediated plasminogen binding is essential for the virulence of an invasiveStreptococcus pyogenesisolate
- 19 March 2008
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 22 (8), 2715-2722
- https://doi.org/10.1096/fj.07-105643
Abstract
The human protease plasmin plays a crucial role in the capacity of the group A streptococcus (GAS; Streptococus pyogenes) to initiate invasive disease. The GAS strain NS88.2 was isolated from a case of bacteremia from the Northern Territory of Australia, a region with high rates of GAS invasive disease. Mutagenesis of the NS88.2 plasminogen binding M protein Prp was undertaken to examine the contribution of plasminogen binding and cell surface plasmin acquisition to virulence. The isogenic mutant NS88.2prp was engineered whereby four amino acid residues critical for plasminogen binding were converted to alanine codons in the GAS genome sequence. The mutated residues were reverse complemented to the wild-type sequence to construct GAS strain NS88.2prpRC. In comparison to NS88.2 and NS88.2prpRC, the NS88.2prp mutant exhibited significantly reduced ability to bind human plasminogen and accumulate cell surface plasmin activity during growth in human plasma. Utilizing a humanized plasminogen mouse model of invasive infection, we demonstrate that the capacity to bind plasminogen and accumulate surface plasmin activity plays an essential role in GAS virulence.—Sanderson-Smith, M. L., Dinkla, K., Cole, J. N., Cork, A. J., Maamary, P. G., McArthur, J. D., Chhatwal, G. S., Walker, M. J. M protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate.Keywords
This publication has 46 references indexed in Scilit:
- Detection of Genes Encoding Internalization-Associated Proteins in Streptococcus pyogenes Isolates from Patients with Invasive Diseases and Asymptomatic CarriersJournal of Clinical Microbiology, 2007
- The Plasminogen-Binding Group A Streptococcal M Protein-Related Protein Prp Binds Plasminogen via Arginine and Histidine ResiduesJournal of Bacteriology, 2007
- The Maintenance of High Affinity Plasminogen Binding by Group A Streptococcal Plasminogen-binding M-like Protein Is Mediated by Arginine and Histidine Residues within the a1 and a2 Repeat DomainsOnline Journal of Public Health Informatics, 2006
- Is plasminogen deployed as a Streptococcus pyogenes virulence factor?Trends in Microbiology, 2005
- Plasminogen Binding by Group A Streptococcal Isolates from a Region of Hyperendemicity for Streptococcal Skin Infection and a High Incidence of Invasive InfectionInfection and Immunity, 2004
- Plasminogen Enhances Virulence of Group A Streptococci by Streptokinase‐Dependent and Streptokinase‐Independent MechanismsThe Journal of Infectious Diseases, 2003
- Plasminogen binding and cancer promises and pitfallsFrontiers in Bioscience-Landmark, 2003
- A Role For Fibrinogen In The Streptokinase-Dependent Acquisition Of Plasmin(ogen) By Group A StreptococciThe Journal of Infectious Diseases, 1995
- Structural heterogeneity of the emm gene cluster in group A streptococciMolecular Microbiology, 1993
- A major surface protein on group A streptococci is a glyceraldehyde-3-phosphate-dehydrogenase with multiple binding activity.The Journal of Experimental Medicine, 1992