Molecular co-operation between protein PAM and streptokinase for plasmin acquisition by Streptococcus pyogenes
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Molecular co-operation between protein PAM and streptokinase for plasmin acquisition by Streptococcus pyogenes. / Ringdahl, U; Svensson, M; Wistedt, A C; Renné, T; Kellner, R; Müller-Esterl, W; Sjöbring, U.
in: J BIOL CHEM, Jahrgang 273, Nr. 11, 13.03.1998, S. 6424-30.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Molecular co-operation between protein PAM and streptokinase for plasmin acquisition by Streptococcus pyogenes
AU - Ringdahl, U
AU - Svensson, M
AU - Wistedt, A C
AU - Renné, T
AU - Kellner, R
AU - Müller-Esterl, W
AU - Sjöbring, U
PY - 1998/3/13
Y1 - 1998/3/13
N2 - 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.
AB - 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.
KW - Antigens, Bacterial
KW - Bacterial Outer Membrane Proteins
KW - Bacterial Proteins
KW - Carrier Proteins
KW - Fibrinolysin
KW - Plasminogen
KW - Recombinant Fusion Proteins
KW - Streptococcus pyogenes
KW - Streptokinase
KW - Transformation, Bacterial
M3 - SCORING: Journal article
C2 - 9497374
VL - 273
SP - 6424
EP - 6430
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 11
ER -