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