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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 LU ; Sjöbring, Ulf LU and Ranson, Marie, et al. (2008) In The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22(9). p.3146-3153
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... (More)
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.-McArthur, J. D., McKay, F. C., Ramachandran, V., Shyam, P., Cork, A. J., Sanderson-Smith, M. L., Cole, J. N., Ringdahl, U., Sjöbring, U., Ranson, M., Walker, M. J. Allelic variants of streptokinase from Streptococcus pyogenes display functional differences in plasminogen activation. (Less)
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The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
volume
22
issue
9
pages
3146 - 3153
publisher
The Federation of American Societies for Experimental Biology
external identifiers
  • WOS:000258761300007
  • PMID:18511548
  • Scopus:51349138787
ISSN
1530-6860
DOI
10.1096/fj.08-109348
language
English
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yes
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f17b7061-3cac-48ba-ae43-0b866ada5e41 (old id 1153686)
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http://www.ncbi.nlm.nih.gov/pubmed/18511548?dopt=Abstract
date added to LUP
2008-06-02 10:36:23
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2016-11-01 10:02:50
@misc{f17b7061-3cac-48ba-ae43-0b866ada5e41,
  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.-McArthur, J. D., McKay, F. C., Ramachandran, V., Shyam, P., Cork, A. J., Sanderson-Smith, M. L., Cole, J. N., Ringdahl, U., Sjöbring, U., Ranson, M., Walker, M. J. Allelic variants of streptokinase from Streptococcus pyogenes display functional differences in plasminogen activation.},
  author       = {McArthur, Jason D and McKay, Fiona C and Ramachandran, Vidiya and Shyam, Priya and Cork, Amanda J and Sanderson-Smith, Martina L and Cole, Jason N and Ringdahl, Ulrika and Sjöbring, Ulf and Ranson, Marie and Walker, Mark J},
  issn         = {1530-6860},
  language     = {eng},
  number       = {9},
  pages        = {3146--3153},
  publisher    = {ARRAY(0x8e414d8)},
  series       = {The FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
  title        = {Allelic variants of streptokinase from Streptococcus pyogenes display functional differences in plasminogen activation.},
  url          = {http://dx.doi.org/10.1096/fj.08-109348},
  volume       = {22},
  year         = {2008},
}