Unité de Biologie des Spirochètes, Institut Pasteur, Paris, France.
University of Victoria - Genome British Columbia Proteomics Centre, Vancouver Island Technology Park, Victoria, British Columbia, Canada.
Cell Microbiol. 2019 Feb;21(2):e12949. doi: 10.1111/cmi.12949. Epub 2018 Sep 26.
Pathogenic Leptospira bacteria are the causative agents of leptospirosis, a zoonotic disease affecting animals and humans worldwide. These pathogenic species have the ability to rapidly cross host tissue barriers by a yet unknown mechanism. A comparative analysis of pathogens and saprophytes revealed a higher abundance of genes encoding proteins with leucine-rich repeat (LRR) domains in the genomes of pathogens. In other bacterial pathogens, proteins with LRR domains have been shown to be involved in mediating host cell attachment and invasion. One protein from the pathogenic species Leptospira interrogans, LIC10831, has been previously analysed via X-ray crystallography, with findings suggesting it may be an important bacterial adhesin. Herein we show that LIC10831 elicits an antibody response in infected animals, is actively secreted by the bacterium, and binds human E- and VE-cadherins. These results provide biochemical and cellular evidences of LRR protein-mediated host-pathogen interactions and identify a new multireceptor binding protein from this infectious Leptospira species.
致病钩端螺旋体细菌是钩端螺旋体病的病原体，这种人畜共患疾病影响着全球的动物和人类。这些致病物种具有通过未知机制快速跨越宿主组织屏障的能力。对病原体和腐生物的比较分析表明，在病原体的基因组中，编码富含亮氨酸重复（LRR）结构域的蛋白质的基因更为丰富。在其他细菌病原体中，具有 LRR 结构域的蛋白质已被证明参与介导宿主细胞附着和入侵。来自致病性物种问号钩端螺旋体的一种蛋白质 LIC10831 之前已经通过 X 射线晶体学进行了分析，研究结果表明它可能是一种重要的细菌黏附素。本文中，我们证明了 LIC10831 在感染动物中引起抗体反应，被细菌主动分泌，并与人类 E-和 VE-钙黏蛋白结合。这些结果提供了 LRR 蛋白介导的宿主-病原体相互作用的生化和细胞证据，并从这种感染性钩端螺旋体物种中鉴定出一种新的多受体结合蛋白。
