Silva Igor R M, Takahashi Maria B, Teixeira Aline F, Nascimento Ana L T O
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, Brazil.
FEBS Open Bio. 2025 Mar;15(3):447-461. doi: 10.1002/2211-5463.13942. Epub 2024 Dec 12.
Pathogenic Leptospira is the etiological cause of the zoonotic life-threatening infection called leptospirosis. The disease is spread worldwide with higher risk in tropical regions. Although leptospirosis represents a burden to the health of humans and animals, the pathogenic mechanisms of Leptospira infection are yet to be clarified. Leptospirosis infection is multifactorial, involving functionally redundant proteins with the capability to invade, disseminate, and escape the host's immune response. In this work, we describe a putative lipoprotein encoded by the gene LIC_13355, genome annotated as hypothetical of unknown function. The coding sequence is conserved among pathogenic Leptospira spp. with high percentage of coverage and identity. The recombinant protein, rLIC_13355, was expressed in Escherichia coli host system in its insoluble form. The circular dichroism spectrum of the refolded protein showed it containing a mixture of secondary structures. rLIC_13355 interacts with extracellular matrix (ECM) component laminin and binds plasminogen (PLG), generating plasmin (PLA), thus possibly participating during the adhesion and dissemination processes. The rLIC_13355 has the ability to interact with Ea.hy926 and HMEC-1 endothelial cells either in monolayer or suspension. The binding of rLIC_13355 with monolayer cells is dose-dependent on protein concentration. Taken together, our data suggest that this is presumably an adhesion lipoprotein that may play diverse roles in host-Leptospira interactions by mediating the interaction with host components and with endothelial cell.
致病性钩端螺旋体是导致钩端螺旋体病这种人畜共患的危及生命感染的病原体。该疾病在全球范围内传播,在热带地区风险更高。尽管钩端螺旋体病给人类和动物的健康带来负担,但钩端螺旋体感染的致病机制尚未阐明。钩端螺旋体感染是多因素的,涉及功能冗余的蛋白质,这些蛋白质具有侵入、传播和逃避宿主免疫反应的能力。在这项研究中,我们描述了一种由基因LIC_13355编码的假定脂蛋白,该基因在基因组中被注释为功能未知的假设蛋白。该编码序列在致病性钩端螺旋体菌种中保守,具有高覆盖率和高同一性。重组蛋白rLIC_13355在大肠杆菌宿主系统中以不溶性形式表达。复性蛋白的圆二色光谱表明它含有多种二级结构的混合物。rLIC_13355与细胞外基质(ECM)成分层粘连蛋白相互作用并结合纤溶酶原(PLG),产生纤溶酶(PLA),因此可能在黏附和传播过程中发挥作用。rLIC_13355能够与单层或悬浮状态的Ea.hy926和HMEC-1内皮细胞相互作用。rLIC_13355与单层细胞的结合呈剂量依赖性,取决于蛋白质浓度。综上所述,我们的数据表明,这可能是一种黏附脂蛋白,通过介导与宿主成分和内皮细胞的相互作用,可能在宿主与钩端螺旋体的相互作用中发挥多种作用。