M protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate

Sanderson-Smith, M. L., Dinkla, K., Cole, J. N., Cork, A. J., Maamary, P. G., McArthur, J. D., Chhatwal, G. S. and Walker, M. J. (2008) M protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate. The FASEB Journal, 22 8: 2715-2722. doi:10.1096/fj.07-105643


Author Sanderson-Smith, M. L.
Dinkla, K.
Cole, J. N.
Cork, A. J.
Maamary, P. G.
McArthur, J. D.
Chhatwal, G. S.
Walker, M. J.
Title M protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate
Formatted title
M protein-mediated plasminogen binding is essential for the virulence of an invasive Streptococcus pyogenes isolate
Journal name The FASEB Journal   Check publisher's open access policy
ISSN 0014-9446
0892-6638
1530-6860
Publication date 2008-08-01
Sub-type Article (original research)
DOI 10.1096/fj.07-105643
Volume 22
Issue 8
Start page 2715
End page 2722
Total pages 8
Place of publication Bethesda, MD, U.S.A.
Publisher Federation of American Societies for Experimental Biology
Language eng
Formatted 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.
Keyword Plasmin
Group A streptococcus
Innate immunity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Chemistry and Molecular Biosciences
 
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Created: Wed, 21 Sep 2011, 00:35:03 EST by Amanda Cork on behalf of School of Chemistry & Molecular Biosciences