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First published online 26 April 2005
doi: 10.1242/jcs.02328

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Cellular invasion by Staphylococcus aureus reveals a functional link between focal adhesion kinase and cortactin in integrin-mediated internalisation

¹ Zentrum für Infektionsforschung, Universität Würzburg, Röntgenring 11, 97070 Würzburg, Germany
² Institut für Molekulare Infektionsbiologie, Universität Würzburg, Röntgenring 11, 97070 Würzburg, Germany
³ Gesellschaft für Biotechnologische Forschung, Mascheroder Weg 1, 38124 Braunschweig, Germany

^* Author for correspondence (e-mail: christof.hauck{at}mail.uni-wuerzburg.de)

Accepted 15 February 2005

Nosocomial infections by Staphylococcus aureus, a Gram-positive pathogen colonising human skin and mucosal surfaces, are an increasing health care problem. Clinical isolates almost invariably express fibronectin-binding proteins that, by indirectly linking the bacteria with host integrin ₅ß₁, can promote uptake of the microorganisms by eukaryotic cells. Integrin engagement by pathogenic fibronectin-binding S. aureus, but not by non-pathogenic S. carnosus, triggered the recruitment of focal contact-associated proteins vinculin, tensin, zyxin and FAK to the sites of bacterial attachment. Moreover, dominant-negative versions of FAK-blocked integrin-mediated internalisation and FAK-deficient cells were severely impaired in their ability to internalise S. aureus. Pathogen binding induced tyrosine phosphorylation of several host proteins associated with bacterial attachment sites, including FAK and the Src substrate cortactin. In FAK-deficient cells, local recruitment of cortactin still occurred, whereas the integrin- and Src-dependent tyrosine phosphorylation of cortactin was abolished. As siRNA-mediated gene silencing of cortactin or mutation of critical amino acid residues within cortactin interfered with uptake of S. aureus, our results reveal a novel functional connection between integrin engagement, FAK activation and Src-mediated cortactin phosphorylation. Cooperation between FAK, Src and cortactin in integrin-mediated internalisation of bacteria also suggests a molecular scenario of how engagement of integrins could be coupled to membrane endocytosis.

Key words: Actin cytoskeleton, Fibronectin, Staphylococci, Focal complexes, Focal adhesion kinase, Cortactin

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