Allelic variants of streptokinase from Streptococcus pyogenes display functional differences in plasminogen activation

McArthur, Jason D., McKay, Fiona C., Ramachandran, Vidiya, Shyam, Priya, Cork, Amanda J., Sanderson-Smith, Martina L., Cole, Jason N., Ringdahl, Ulrika, Sjobring, Ulf, Ranson, Marie and Walker, Mark J. (2008) Allelic variants of streptokinase from Streptococcus pyogenes display functional differences in plasminogen activation. Faseb Journal, 22 9: 3146-3153. doi:10.1096/fj.08-109348


Author McArthur, Jason D.
McKay, Fiona C.
Ramachandran, Vidiya
Shyam, Priya
Cork, Amanda J.
Sanderson-Smith, Martina L.
Cole, Jason N.
Ringdahl, Ulrika
Sjobring, Ulf
Ranson, Marie
Walker, Mark J.
Title Allelic variants of streptokinase from Streptococcus pyogenes display functional differences in plasminogen activation
Journal name Faseb Journal   Check publisher's open access policy
ISSN 0892-6638
Publication date 2008-09
Sub-type Article (original research)
DOI 10.1096/fj.08-109348
Volume 22
Issue 9
Start page 3146
End page 3153
Total pages 8
Place of publication United States
Publisher Federation of American Societies for Experimental Biology
Language eng
Abstract A common mammalian defense mechanism employed to prevent systemic dissemination of invasive bacteria involves occlusion of local microvasculature and encapsulation of bacteria within fibrin networks. Acquisition of plasmin activity at the bacterial cell surface circumvents this defense mechanism, allowing invasive disease initiation. To facilitate this process, S. pyogenes secretes streptokinase, a plasminogen-activating protein. Streptokinase polymorphism exhibited by S. pyogenes isolates is well characterized. However, the functional differences displayed by these variants and the biological significance of this variation has not been elucidated. Phylogenetic analysis of ska sequences from 28 S. pyogenes isolates revealed 2 main sequence clusters (clusters 1 and 2). All strains secreted streptokinase, as determined by Western blotting, and were capable of acquiring cell surface plasmin activity after incubation in human plasma. Whereas culture supernatants from strains containing cluster 1 ska alleles also displayed soluble plasminogen activation activity, supernatants from strains containing cluster 2 ska alleles did not. Furthermore, plasminogen activation activity in culture supernatants from strains containing cluster 2 ska alleles could only be detected when plasminogen was prebound with fibrinogen. This study indicates that variant streptokinase proteins secreted by S. pyogenes isolates display differing plasminogen activation characteristics and may therefore play distinct roles in disease pathogenesis.
Keyword Bacterial pathogenesis
Virulence
Invasive disease
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
School of Chemistry and Molecular Biosciences
 
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