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Fluid Shear Regulates the Kinetics and Receptor Specificity of Staphylococcus aureus Binding to Activated Platelets¹

Parag Pawar^*, Pyong Kyun Shin, Shaker A. Mousa, Julia M. Ross and Konstantinos Konstantopoulos^2,*

^* Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218; Department of Chemical and Biochemical Engineering, University of Maryland Baltimore County, Baltimore, MD 21250; and Albany College of Pharmacy and Pharmaceutical Research Institute, Albany, NY 12208

The interaction between surface components on the invading pathogen and host cells such as platelets plays a key role in the regulation of endovascular infections. However, the mechanisms mediating Staphylococcus aureus binding to platelets under shear remain largely unknown. This study was designed to investigate the kinetics and molecular requirements of platelet-S. aureus interactions in bulk suspensions subjected to a uniform shear field. Hydrodynamic shear-induced collisions augment platelet-S. aureus binding, which is further potentiated by platelet activation with stromal derived factor-1. Peak adhesion efficiency occurs at low shear (100 s^–1) and decreases with increasing shear. The molecular interaction of platelet _IIb3 with bacterial clumping factor A through fibrinogen bridging is necessary for stable bacterial binding to activated platelets under shear. Although this pathway is sufficient at low shear (400 s^–1), the involvement of platelet gpIb and staphylococcal protein A through von Willebrand factor bridging is essential for optimal recruitment of S. aureus cells by platelets in the high shear regime. IgG plays an inhibitory role in the adhesion process, presumably by interfering with the binding of von Willebrand factor to staphylococcal protein A. This study demonstrates that platelet activation and a fluid-mechanical environment representative of the vasculature affect platelet-S. aureus cell-adhesive interactions pertinent to the process of S. aureus-induced bloodstream infections.

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