|
|
|
|
|
||
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online 26 April 2005
doi: 10.1242/jcs.02328
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
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
This article has been cited by other articles:
|
|
 |
|
  S. Bergmann, A. Lang, M. Rohde, V. Agarwal, C. Rennemeier, C. Grashoff, K. T. Preissner, and S. Hammerschmidt Integrin-linked kinase is required for vitronectin-mediated internalization of Streptococcus pneumoniae by host cells J. Cell Sci., January 15, 2009; 122(2): 256 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ricciuto, S. R. Heimer, M. S. Gilmore, and P. Argueso Cell Surface O-Glycans Limit Staphylococcus aureus Adherence to Corneal Epithelial Cells Infect. Immun., November 1, 2008; 76(11): 5215 - 5220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Farfan, K. G. Inman, and J. P. Nataro The Major Pilin Subunit of the AAF/II Fimbriae from Enteroaggregative Escherichia coli Mediates Binding to Extracellular Matrix Proteins Infect. Immun., October 1, 2008; 76(10): 4378 - 4384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Horn, S. M. Knecht, F. L. Rushing, J. Birdsong, C. P. Siddall, C. M. Johnson, T. N. Abraham, A. Brown, C. B. Volk, K. Gammon, et al. Simvastatin Inhibits Staphylococcus aureus Host Cell Invasion through Modulation of Isoprenoid Intermediates J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 135 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Dupuy and E. Caron Integrin-dependent phagocytosis - spreading from microadhesion to new concepts J. Cell Sci., June 1, 2008; 121(11): 1773 - 1783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Galka, S. N. Wai, H. Kusch, S. Engelmann, M. Hecker, B. Schmeck, S. Hippenstiel, B. E. Uhlin, and M. Steinert Proteomic Characterization of the Whole Secretome of Legionella pneumophila and Functional Analysis of Outer Membrane Vesicles Infect. Immun., May 1, 2008; 76(5): 1825 - 1836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Sangrar, Y. Gao, M. Scott, P. Truesdell, and P. A. Greer Fer-Mediated Cortactin Phosphorylation Is Associated with Efficient Fibroblast Migration and Is Dependent on Reactive Oxygen Species Generation during Integrin-Mediated Cell Adhesion Mol. Cell. Biol., September 1, 2007; 27(17): 6140 - 6152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tehrani, N. Tomasevic, S. Weed, R. Sakowicz, and J. A. Cooper Src phosphorylation of cortactin enhances actin assembly PNAS, July 17, 2007; 104(29): 11933 - 11938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Schroder, B. Schroder, B. Roppenser, S. Linder, B. Sinha, R. Fassler, and M. Aepfelbacher Staphylococcus aureus Fibronectin Binding Protein-A Induces Motile Attachment Sites and Complex Actin Remodeling in Living Endothelial Cells Mol. Biol. Cell, December 1, 2006; 17(12): 5198 - 5210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shi and J. E. Casanova Invasion of Host Cells by Salmonella typhimurium Requires Focal Adhesion Kinase and p130Cas Mol. Biol. Cell, November 1, 2006; 17(11): 4698 - 4708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Pellinen and J. Ivaska Integrin traffic. J. Cell Sci., September 15, 2006; 119(Pt 18): 3723 - 3731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ouhara, H. Komatsuzawa, H. Shiba, Y. Uchida, T. Kawai, K. Sayama, K. Hashimoto, M. A. Taubman, H. Kurihara, and M. Sugai Actinobacillus actinomycetemcomitans Outer Membrane Protein 100 Triggers Innate Immunity and Production of {beta}-Defensin and the 18-Kilodalton Cationic Antimicrobial Protein through the Fibronectin-Integrin Pathway in Human Gingival Epithelial Cells Infect. Immun., September 1, 2006; 74(9): 5211 - 5220. [Abstract] [Full Text] [PDF]
|
|
