Fibronectin binding proteins contribute to the adherence of Staphylococcus aureus to intact endothelium in vivo

Sylvain Kerdudou; Matthias W. Laschke; Bhanu Sinha; Klaus T. Preissner; Michael D. Menger; Mathias Herrmann

doi:10.1160/TH06-02-0116

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(02): 183-189
DOI: 10.1160/TH06-02-0116

Wound Healing and Inflammation/Infection

Schattauer GmbH

Fibronectin binding proteins contribute to the adherence of Staphylococcus aureus to intact endothelium in vivo

Authors

Sylvain Kerdudou^*

¹Institute of Medical Microbiology and Hygiene, University of Saarland Hospital, Homburg/Saar, Germany
Matthias W. Laschke^*

²Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
Bhanu Sinha

³Institute of Medical Microbiology, University Hospital of Münster, Münster, Germany
Klaus T. Preissner

⁴Institute of Biochemistry University Giessen, Giessen, Germany
Michael D. Menger

²Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany
Mathias Herrmann

¹Institute of Medical Microbiology and Hygiene, University of Saarland Hospital, Homburg/Saar, Germany

Abstract

Summary

Staphylococcal adhesins mediate attachment to matrix proteins and endothelial cells in vitro, yet, their role in primary adherence to the physiologic vessel wall has not been studied in vivo, and complex endocarditis models yielded ambiguous results. Recently, we developed a hamster model to study interaction kinetics of S. aureus with intact microvasculature using intravital fluorescence microscopy (Laschke et al. J Infect Dis 2005; 191: 435-43) providing the basis for this study. S. aureus Cowan 1 wild type (WT) log phase cells adhered to postcapillary venules to a significantly larger extent compared to stationary phase staphylococci, a finding in congruence with the fact that the staphylococcal adhesin repertoire largely depends on the growth phase. In comparison, the adherence rate of the fnbA deleted mutant (DU5895) to the vessel wall was significantly reduced to approximately 40% of WT. These DU5895 attachment rates were similar to those of an S. carnosus strain (TM300). In contrast, upon heterologous complementation of TM300 with either fnbA and fnbB, adherence of these transformants to the microvasculature increased, an increase found to be significant for fnbA transformant single cocci and clusters at 30 and 60 min when compared to S. carnosus TM300 WT. In conclusion, these results demonstrate that staphylococcal FnBPs significantly contribute to primary interaction with intact endothelium under physiologic conditions. Accordingly, this attribution of staphylococcal FnBPs providea rationale for novel intervention strategies such as the use of anti-FnBP antibodies in endovascular S. aureus disease.

Keywords

Staphylococcus aureus - endothelium - intravital fluorescence microscopy - fibronectin binding protein A - adherence

Full Text

References

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