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First published online December 31, 2008
doi: 10.1242/10.1242/jcs.035600

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Integrin-linked kinase is required for vitronectin-mediated internalization of Streptococcus pneumoniae by host cells

Simone Bergmann^1,2, Anke Lang², Manfred Rohde³, Vaibhav Agarwal^1,*, Claudia Rennemeier^2,, Carsten Grashoff^4,, Klaus T. Preissner⁵ and Sven Hammerschmidt^1,2,¶,**

¹ Max von Pettenkofer-Institute for Hygiene and Medical Microbiology, Ludwig-Maximilians University, Pettenkoferstrasse 9a, 80336 München, Germany
² University of Würzburg, Research Center for Infectious Diseases, Röntgenring 11, 97070 Würzburg, Germany
³ Department of Microbial Pathogenesis, Helmholtz Center for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany
⁴ Department of Molecular Medicine, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany
⁵ Institute for Biochemistry, Justus-Liebig-University, Friedrichstrasse 24, 35392 Giessen, Germany

^** Author for correspondence (e-mail: sven.hammerschmidt{at}uni-greifswald.de)

Accepted 6 October 2008

By interacting with components of the human host, including extracellular matrix (ECM) proteins, Streptococcus pneumoniae has evolved various strategies for colonization. Here, we characterized the interaction of pneumococci with the adhesive glycoprotein vitronectin and the contribution of this protein to pneumococcal uptake by host cells in an integrin-dependent manner. Specific interaction of S. pneumoniae with the heparin-binding sites of purified multimeric vitronectin was demonstrated by flow cytometry analysis. Host-cell-bound vitronectin promoted pneumococcal adherence to and invasion into human epithelial and endothelial cells. Pneumococci were trapped by microspike-like structures, which were induced upon contact of pneumococci with host-cell-bound vitronectin. vβ3 integrin was identified as the major cellular receptor for vitronectin-mediated adherence and uptake of pneumococci. Ingestion of pneumococci by host cells via vitronectin required a dynamic actin cytoskeleton and was dependent on integrin-linked kinase (ILK), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt), as demonstrated by gene silencing or in inhibition experiments. In conclusion, pneumococci exploit the vitronectin–vβ3-integrin complex as a cellular receptor for invasion and this integrin-mediated internalization requires the cooperation between the host signalling molecules ILK, PI3K and Akt.

Key words: Pneumococci, Vitronectin, Invasion, Integrin, ILK, Akt, Microspikes

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