Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
CÚRAM-Centre for Research in Medical Devices, National University of Ireland Galway, Galway, Ireland.
FEMS Microbiol Lett. 2019 May 1;366(9). doi: 10.1093/femsle/fnz107.
Prevention of device related infections due to Staphylococcus aureus biofilms on devices represents a significant challenge. Such infections have recently been shown to be dependent on the coagulation pathway via activation of pro-thrombin and fibrin production. Three direct-thrombin inhibitors, argatroban, hirudin and dabigatran, were examined to determine their effect on preventing S. aureus biofilm on plastic biochip surfaces under shear stress using an in vivo relevant model of infection. Surface functionalization of polyurethane discs via dityrosine covalent crosslinking with hirudin was performed and changes in bacterial density and microscopic appearances determined. The three direct-thrombin inhibitors prevented S. aureus biofilm formation on plasma-coated surfaces treated with these agents. Coating of polyurethane with one of these agents, hirudin, significantly inhibited biofilm formation on the modified surface. These findings reveal the exciting potential for coating biomaterial surfaces with direct thrombin inhibitors to prevent staphylococcal binding and subsequent device-related infections.
预防金黄色葡萄球菌生物膜引起的装置相关感染是一个重大挑战。最近的研究表明，这种感染依赖于凝血途径，通过激活凝血酶原和纤维蛋白生成。本研究检测了三种直接凝血酶抑制剂（argatroban、水蛭素和达比加群），以确定它们在体内相关感染模型下，对剪切应力下塑料生物芯片表面金黄色葡萄球菌生物膜形成的影响。通过二酪氨酸共价交联与水蛭素对聚氨酯圆盘进行表面功能化，并确定细菌密度和微观外观的变化。这三种直接凝血酶抑制剂可预防用这些药物处理的血浆涂层表面上的金黄色葡萄球菌生物膜形成。用这些试剂之一水蛭素来涂覆聚氨酯，可显著抑制改性表面上的生物膜形成。这些发现揭示了用直接凝血酶抑制剂涂覆生物材料表面以防止葡萄球菌结合和随后的器械相关感染的令人兴奋的潜力。
