Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil.
Programa de Pós-Graduação Interunidades Em Biotecnologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
Virulence. 2021 Dec;12(1):2798-2813. doi: 10.1080/21505594.2021.1993427.
Leptospirosis is a globally prevalent zoonotic disease, and is caused by pathogenic spirochetes from the genus . LipL21 and LipL41 are lipoproteins expressed strongly on the outer membrane of pathogenic spp. Many studies have shown that both proteins are interesting targets for vaccines and diagnosis. However, their role in host-pathogen interactions remains underexplored. Therefore, we evaluated the capacity of LipL21 and LipL41 to bind with glycosaminoglycans (GAGs), the cell receptors and extracellular matrix, and plasma components by ELISA. Both proteins interacted with collagen IV, laminin, E-cadherin, and elastin dose-dependently. A broad-spectrum binding to plasma components was also observed. Only LipL21 interacted with all the GAG components tested, whereas LipL41 presented a concentration-dependent binding only for chondroitin 4 sulfate. Although, both proteins have the ability to interact with fibrinogen, only LipL21 inhibited fibrin clot formation partially. Both proteins exhibited a decrease in plasminogen binding in the presence of amino caproic acid (ACA), a competitive inhibitor of lysine residues, suggesting that their binding occurs via the kringle domains of plasminogen. LipL41, but not LipL21, was able to convert plasminogen to plasmin, and recruit plasminogen from normal human serum, suggesting that the interaction of this protein with plasminogen may occur in physiological conditions. This work provides the first report demonstrating the capacity of LipL21 and LipL41 to interact with a broad range of host components, highlighting their importance in host- interactions.
钩端螺旋体病是一种全球性流行的动物源性传染病，由属的致病性螺旋体引起。LipL21 和 LipL41 是致病性 spp. 外膜上强烈表达的脂蛋白。许多研究表明，这两种蛋白都是疫苗和诊断的有趣靶点。然而，它们在宿主-病原体相互作用中的作用仍未得到充分探索。因此，我们通过 ELISA 评估了 LipL21 和 LipL41 与糖胺聚糖（GAGs）、细胞受体和细胞外基质以及血浆成分结合的能力。两种蛋白均与胶原蛋白 IV、层粘连蛋白、E-钙黏蛋白和弹性蛋白呈剂量依赖性相互作用。还观察到与广谱血浆成分的结合。只有 LipL21 与所有测试的 GAG 成分相互作用，而 LipL41 仅表现出与硫酸软骨素 4 的浓度依赖性结合。尽管两种蛋白都有与纤维蛋白原相互作用的能力，但只有 LipL21 部分抑制纤维蛋白凝块的形成。在赖氨酸竞争抑制剂氨基己酸（ACA）存在的情况下，两种蛋白的纤溶酶原结合均减少，表明它们的结合通过纤溶酶原的kringle 结构域发生。LipL41 但不是 LipL21 能够将纤溶酶原转化为纤溶酶，并从正常人血清中募集纤溶酶原，表明该蛋白与纤溶酶原的相互作用可能发生在生理条件下。这项工作首次报道了 LipL21 和 LipL41 与广泛宿主成分相互作用的能力，强调了它们在宿主相互作用中的重要性。
