Advanced

Molecular co-operation between protein PAM and streptokinase for plasmin acquisition by Streptococcus pyogenes.

Ringdahl, Ulrika LU ; Svensson, M; Wistedt, AC; Renné, T; Keller, R; Muller-Esterl, W and Sjöbring, Ulf LU (1998) In The Journal of biological chemistry 273(11). p.6424-6430
Abstract
Bacterial surface-associated plasmin formation is believed to contribute to invasion, although the underlying molecular mechanisms are poorly understood. To define the components necessary for plasmin generation on group A streptococci we used strain AP53 which exposes an M-like protein ("PAM") that contains a plasminogen-binding sequence with two 13-amino acid residues long tandem repeats (a1 and a2). Utilizing an Escherichia coli-streptococcal shuttle vector, we replaced a 29-residue long sequence segment of Arp4, an M-like protein that does not bind plasminogen, with a single (a1) or the combined a1a2 repeats of PAM. When expressed in E. coli, the purified chimeric Arp/PAM proteins both bound plasminogen, as well as plasmin, and when... (More)
Bacterial surface-associated plasmin formation is believed to contribute to invasion, although the underlying molecular mechanisms are poorly understood. To define the components necessary for plasmin generation on group A streptococci we used strain AP53 which exposes an M-like protein ("PAM") that contains a plasminogen-binding sequence with two 13-amino acid residues long tandem repeats (a1 and a2). Utilizing an Escherichia coli-streptococcal shuttle vector, we replaced a 29-residue long sequence segment of Arp4, an M-like protein that does not bind plasminogen, with a single (a1) or the combined a1a2 repeats of PAM. When expressed in E. coli, the purified chimeric Arp/PAM proteins both bound plasminogen, as well as plasmin, and when used to transform group A streptococcal strains lacking the plasminogen-binding ability, transformants with the Arp/PAM constructs efficiently bound plasminogen. Moreover, when grown in the presence of plasminogen, both Arp/PAM- and PAM-expressing streptococci acquired surface-bound plasmin. In contrast, plasminogen activation failed to occur on PAM- and Arp/PAM-expressing streptococci carrying an inactivated streptokinase gene: this block was overcome by exogenous streptokinase. Together, these results provide evidence for an unusual co-operation between a surface-bound protein, PAM, and a secreted protein, streptokinase, resulting in bacterial acquisition of a host protease that is likely to spur parasite invasion of host tissues. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of biological chemistry
volume
273
issue
11
pages
6424 - 6430
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • Scopus:0032513149
language
English
LU publication?
yes
id
32619b37-50e8-437f-a810-58ed94456a24 (old id 1216574)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/9497374
http://www.jbc.org/content/273/11/6424.long
date added to LUP
2013-10-09 15:43:53
date last changed
2016-04-16 12:25:57
@misc{32619b37-50e8-437f-a810-58ed94456a24,
  abstract     = {Bacterial surface-associated plasmin formation is believed to contribute to invasion, although the underlying molecular mechanisms are poorly understood. To define the components necessary for plasmin generation on group A streptococci we used strain AP53 which exposes an M-like protein ("PAM") that contains a plasminogen-binding sequence with two 13-amino acid residues long tandem repeats (a1 and a2). Utilizing an Escherichia coli-streptococcal shuttle vector, we replaced a 29-residue long sequence segment of Arp4, an M-like protein that does not bind plasminogen, with a single (a1) or the combined a1a2 repeats of PAM. When expressed in E. coli, the purified chimeric Arp/PAM proteins both bound plasminogen, as well as plasmin, and when used to transform group A streptococcal strains lacking the plasminogen-binding ability, transformants with the Arp/PAM constructs efficiently bound plasminogen. Moreover, when grown in the presence of plasminogen, both Arp/PAM- and PAM-expressing streptococci acquired surface-bound plasmin. In contrast, plasminogen activation failed to occur on PAM- and Arp/PAM-expressing streptococci carrying an inactivated streptokinase gene: this block was overcome by exogenous streptokinase. Together, these results provide evidence for an unusual co-operation between a surface-bound protein, PAM, and a secreted protein, streptokinase, resulting in bacterial acquisition of a host protease that is likely to spur parasite invasion of host tissues.},
  author       = {Ringdahl, Ulrika and Svensson, M and Wistedt, AC and Renné, T and Keller, R and Muller-Esterl, W and Sjöbring, Ulf},
  language     = {eng},
  number       = {11},
  pages        = {6424--6430},
  publisher    = {ARRAY(0x91712d8)},
  series       = {The Journal of biological chemistry},
  title        = {Molecular co-operation between protein PAM and streptokinase for plasmin acquisition by Streptococcus pyogenes.},
  volume       = {273},
  year         = {1998},
}