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Infection and Immunity, February 2008, p. 466-476, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.01261-07
Copyright © 2008, American Society for Microbiology. 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, CNRS, CEA, and Université Joseph Fourier, Partnership for Structural Biology, F-38027 Grenoble, France

Received 13 September 2007/ Returned for modification 18 October 2007/ Accepted 27 November 2007

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 protein family) as an important receptor for human plasminogen, the precursor of plasmin. The results of ligand overlay blot analyses, solid-phase binding assays, and surface plasmon resonance experiments support the idea of an interaction between CBPE and plasminogen. We have shown that the phosphorylcholine esterase (Pce) domain of CBPE interacts with the plasminogen kringle domains. 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, compared to the wild-type strain, a mutant of pneumococcus with the cbpE gene deleted (i) displays a reduced level of plasminogen binding and plasmin activation and (ii) shows reduced ability to cross the extracellular matrix in an in vitro model. These results support the idea of a physiological role for the CBPE-plasminogen interaction in pneumococcal dissemination into human tissue.

Published ahead of print on 10 December 2007.

Editor: J. N. Weiser

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• Attali, C., Durmort, C., Vernet, T., Di Guilmi, A. M. (2008). The Interaction of Streptococcus pneumoniae with Plasmin Mediates Transmigration across Endothelial and Epithelial Monolayers by Intercellular Junction Cleavage. Infect. Immun. 76: 5350-5356 [Abstract] [Full Text]