Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India.
ACS Infect Dis. 2024 Sep 13;10(9):3256-3272. doi: 10.1021/acsinfecdis.4c00266. Epub 2024 Sep 4.
The survival and proliferation of pathogenic within a host are complex phenomena that require careful consideration. The ErpY-like lipoprotein, found on the outer membrane surface of , plays a crucial role in enhancing the bacterium's pathogenicity. The rErpY-like protein, in its recombinant form, contributes significantly to spirochete virulence by interacting with various host factors, including host complement regulators. This interaction facilitates the bacterium's evasion of the host complement system, thereby augmenting its overall pathogenicity. The rErpY-like protein exhibits a robust binding affinity to soluble fibrinogen, a vital component of the host coagulation system. In this study, we demonstrate that the rErpY-like protein intervenes in the clotting process of the platelet-poor citrated plasma of bovines and humans in a concentration-dependent manner. It significantly reduces clot density, alters the viscoelastic properties of the clot, and diminishes the average clotting rate in plasma. Furthermore, the ErpY-like protein inhibits thrombin-catalyzed fibrin formation in a dose-dependent manner and exhibits saturable binding to thrombin, suggesting its significant role in leptospiral infection. These findings provide compelling evidence for the anticoagulant effect of the ErpY-like lipoprotein and its significant role in leptospiral infection.
在宿主体内，病原的存活和增殖是复杂的现象，需要仔细考虑。在 的外膜表面发现的 ErpY 样脂蛋白在增强细菌的致病性方面起着至关重要的作用。重组形式的 rErpY 样蛋白通过与包括宿主补体调节因子在内的各种宿主因子相互作用，显著促进螺旋体的毒力。这种相互作用有助于细菌逃避宿主补体系统，从而增强其整体致病性。rErpY 样蛋白对可溶性纤维蛋白原（宿主凝血系统的重要组成部分）具有很强的结合亲和力。在这项研究中，我们证明 rErpY 样蛋白以浓度依赖的方式干预牛和人血小板贫 citrated 血浆的凝血过程。它显著降低了凝块密度，改变了凝块的粘弹性，并降低了血浆中的平均凝血速率。此外，ErpY 样蛋白以剂量依赖的方式抑制凝血酶催化的纤维蛋白形成，并对凝血酶表现出饱和结合，表明其在钩端螺旋体感染中的重要作用。这些发现为 ErpY 样脂蛋白的抗凝作用及其在钩端螺旋体感染中的重要作用提供了有力证据。
