Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College Dublin, Dublin 2, Ireland.
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Microbiology (Reading). 2010 Mar;156(Pt 3):920-928. doi: 10.1099/mic.0.036673-0. Epub 2009 Dec 10.
The interaction of bacteria with platelets is implicated in the pathogenesis of endovascular infections, including infective endocarditis, of which Staphylococcus aureus is the leading cause. Several S. aureus surface proteins mediate aggregation of platelets by fibrinogen- or fibronectin-dependent processes, which also requires specific antibodies. In this study S. aureus was grown in iron-limited medium to mimic in vivo conditions in which iron is unavailable to pathogens. Under such conditions, a S. aureus mutant lacking the known platelet-activating surface proteins adhered directly to platelets in the absence of plasma proteins and triggered aggregation. Platelet adhesion and aggregation was prevented by inhibiting expression of iron-regulated surface determinant (Isd) proteins. Mutants defective in IsdB, but not IsdA or IsdH, were unable to adhere to or aggregate platelets. Antibodies to the platelet integrin GPIIb/IIIa inhibited platelet adhesion by IsdB-expressing strains, as did antagonists of GPIIb/IIIa. Surface plasmon resonance demonstrated that recombinant IsdB interacts directly with GPIIb/IIIa.
细菌与血小板的相互作用与血管内感染的发病机制有关，包括感染性心内膜炎，其中金黄色葡萄球菌是主要原因。几种金黄色葡萄球菌表面蛋白通过纤维蛋白原或纤维连接蛋白依赖的过程介导血小板聚集，这也需要特定的抗体。在这项研究中，金黄色葡萄球菌在缺铁培养基中生长，以模拟体内病原体无法获得铁的情况。在这种情况下，一种缺乏已知血小板激活表面蛋白的金黄色葡萄球菌突变体在没有血浆蛋白的情况下直接黏附到血小板上，并引发聚集。血小板黏附和聚集可通过抑制铁调节表面决定簇（Isd）蛋白的表达来预防。IsdB 缺陷突变体，但不是 IsdA 或 IsdH 缺陷突变体，无法黏附和聚集血小板。针对血小板整合素 GPIIb/IIIa 的抗体可抑制表达 IsdB 的菌株的血小板黏附，GPIIb/IIIa 的拮抗剂也可抑制。表面等离子体共振显示重组 IsdB 与 GPIIb/IIIa 直接相互作用。
