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Infect. Immun. doi:10.1128/IAI.01261-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Streptococcus pneumoniae Choline-Binding Protein E interaction with plasminogen/plasmin stimulates migration across the extracellular matrix

Institut de Biologie Structurale Jean-Pierre Ebel UMR 5075, Laboratoire d'Ingénierie des Macromolécules, 41 rue Jules Horowitz, F-38027 Grenoble; CEA; CNRS; Université Joseph Fourier, Partnership for Structural Biology

^* To whom correspondence should be addressed. Email: vernet{at}ibs.fr.

	Abstract

The virulence mechanisms leading Streptococcus pneumoniae to convert from nasopharyngeal colonization to a tissue invasive phenotype are still largely unknown. Proliferation of infection requires penetration of the extracellular matrix which occurs by recruitment of host proteases to the bacterial cell surface. We present evidence supporting the role of Choline-Binding Protein E (CBPE) (a member of the surface-exposed Choline-Binding Proteins family) as an important receptor for human plasminogen, the precursor of plasmin. Ligand overlay blots, solid-phase binding assays and Surface Plasmon Resonance experiments support the interaction between CBPE and plasminogen. We have shown that the phosphorylcholine esterase (Pce) domain of CBPE interacts with the plasminogen kringle domains (Lysine-Binding Site-1, LBS-1). Analysis of the crystal structure of the Pce domain, followed by site-directed mutagenesis, allowed the identification of the plasminogen binding region composed in part by lysine residues, some of which map in a linear fashion on the surface of the Pce domain. The biological relevance of the CBPE- plasminogen interaction is supported by the fact that, when compared to the wild type strain, a mutant of pneumococcus deleted for the cbpE gene: (i), displays a reduced level of plasminogen binding and activation into plasmin; (ii), shows a lower ability to cross an in vitro model of the extracellular matrix. These results support a physiological role for the CBPE- plasminogen interaction in pneumococcal dissemination into human tissue.