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Thromb Haemost 2014; 111(03): 401-416
DOI: 10.1160/TH13-05-0421
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Pneumococcal phosphoglycerate kinase interacts with plasminogen and its tissue activator

Marcus Fulde   *
1   Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
2   Current adress: Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany
,
Noelia Bernardo-García   *
3   Department of Crystallograhy and Structural Biology, Instituto de Química-Física “Rocasolano”, CSIC, Madrid, Spain
,
Manfred Rohde
1   Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
,
Nadine Nachtigall
1   Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
,
Ronald Frank
4   Department of Chemical Biology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
,
Klaus T. Preissner
5   Institute for Biochemistry, Justus-Liebig University of Giessen, Giessen, Germany;
,
Javier Klett
6   Unidad de Bioinformática, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Campus UAM, Madrid, Spain
,
Antonio Morreale
6   Unidad de Bioinformática, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Campus UAM, Madrid, Spain
7   Current adress: Repsol, Technology Center, Móstoles, Madrid, Spain
,
G. Singh Chhatwal
1   Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
,
Juan A. Hermoso
3   Department of Crystallograhy and Structural Biology, Instituto de Química-Física “Rocasolano”, CSIC, Madrid, Spain
,
Simone Bergmann
1   Department of Medical Microbiology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany
8   Current adress: Department of Infection Biology, Institute of Microbiology, Technische Universität Braunschweig, Braunschweig, Germany
› Author Affiliations Financial support: The research leading to these results has received funding from the European Community’s Seventh Framework Program under Grant Agreement no. HEALTH-F3–2009–223111. This work was also supported by grants from the Spanish Ministry of Economy and Competitiveness (BFU2011–25326) and Comunidad Autónoma de Madrid (CAM) S2010-BMD-2457 (BIPEDD2). J.K. is funded by a grant from Ministerio de Economía y Competitividad (BFU2011–24595). A.M. also acknowledges CAM for financial support to the Fundación Severo Ochoa through the AMAROUTO program.
Further Information

Publication History

Received: 24 May 2013

Accepted after major revision: 01 October 2013

Publication Date:
22 November 2017 (online)

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Summary

Streptococcus pneumoniae is not only a commensal of the nasopharyngeal epithelium, but may also cause life-threatening diseases. Immune-electron microscopy studies revealed that the bacterial glycolytic enzyme, phosphoglycerate kinase (PGK), is localised on the pneumococcal surface of both capsulated and non-capsulated strains and colocalises with plasminogen. Since pneumococci may concentrate host plasminogen (PLG) together with its activators on the bacterial cell surface to facilitate the formation of plasmin, the involvement of PGK in this process was studied. Specific binding of human or murine PLG to strain-independent PGK was documented, and surface plasmon resonance analyses indicated a high affinity interaction with the kringle domains 1–4 of PLG. Crystal structure determination of pneumococcal PGK together with peptide array analysis revealed localisation of PLG-binding site in the N-terminal region and provided structural motifs for the interaction with PLG. Based on structural analysis data, a potential interaction of PGK with tissue plasminogen activator (tPA) was proposed and experimentally confirmed by binding studies, plasmin activity assays and thrombus degradation analyses.

Keywords

Angiostatin - plasminogen - phosphoglycerate kinase - Streptococcus pneumoniae - tissue-type plasminogen activator

* These authors contributed equally to the work.


 

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