Coumou Jeroen, Narasimhan Sukanya, Trentelman Jos J, Wagemakers Alex, Koetsveld Joris, Ersoz Jasmin I, Oei Anneke, Fikrig Erol, Hovius Joppe W
Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
Department of Internal Medicine, Yale University School of Medicine, 06511, New Haven, CT, USA.
J Mol Med (Berl). 2016 Mar;94(3):361-70. doi: 10.1007/s00109-015-1365-0. Epub 2015 Nov 23.
The causative agent of Lyme borreliosis, Borrelia burgdorferi, is transmitted by Ixodes ticks. During tick feeding, B. burgdorferi migrates from the tick gut to the salivary glands from where transmission to the host occurs. B. burgdorferi-interacting tick proteins might serve as vaccine targets to thwart B. burgdorferi transmission. A previous screening for B. burgdorferi-interacting Ixodes scapularis gut proteins identified an I. scapularis putative dystroglycan protein (ISCW015049). Here, we describe the ISCW015049's protein structure and its cellular location in the tick gut in relation to B. burgdorferi migration. Secondly, in vivo B. burgdorferi-tick attachment murine models were performed to study the role of ISCW015049 during B. burgdorferi migration and transmission. In silico analysis confirmed that ISCW015049 is similar to dystroglycan and was named I. scapularis dystroglycan-like protein (ISDLP). Confocal microscopy of gut tissue showed that ISDLP is expressed on the surface of gut cells, is upregulated during tick feeding, and is expressed significantly higher in infected ticks compared to uninfected ticks. Inhibition of ISDLP by RNA interference (RNAi) resulted in lower B. burgdorferi transmission to mice. In conclusion, we have identified a dystroglycan-like protein in I. scapularis gut that can bind to B. burgdorferi and promotes B. burgdorferi migration from the tick gut. Key messages: B. burgdorferi exploits tick proteins to orchestrate its transmission to the host. B. burgdorferi is able bind to an I. scapularis dystroglycan-like protein (ISDLP). Inhibition of ISDLP in ticks results in lower B. burgdorferi transmission to mice. ISDLP is a potential target to prevent Lyme borreliosis.
莱姆病的病原体伯氏疏螺旋体通过硬蜱传播。在蜱虫进食过程中，伯氏疏螺旋体从蜱虫肠道迁移至唾液腺，进而由此传播至宿主。与伯氏疏螺旋体相互作用的蜱虫蛋白可能成为阻碍伯氏疏螺旋体传播的疫苗靶点。此前对与伯氏疏螺旋体相互作用的肩突硬蜱肠道蛋白进行的筛选鉴定出一种肩突硬蜱假定的营养不良聚糖蛋白（ISCW015049）。在此，我们描述了ISCW015049的蛋白质结构及其在蜱虫肠道中相对于伯氏疏螺旋体迁移的细胞定位。其次，构建了体内伯氏疏螺旋体-蜱虫附着小鼠模型，以研究ISCW015049在伯氏疏螺旋体迁移和传播过程中的作用。计算机分析证实ISCW015049与营养不良聚糖相似，并将其命名为肩突硬蜱营养不良聚糖样蛋白（ISDLP）。肠道组织的共聚焦显微镜检查显示，ISDLP在肠道细胞表面表达，在蜱虫进食期间上调，且与未感染蜱虫相比，在感染蜱虫中的表达显著更高。通过RNA干扰（RNAi）抑制ISDLP会导致伯氏疏螺旋体向小鼠的传播减少。总之，我们在肩突硬蜱肠道中鉴定出一种营养不良聚糖样蛋白，它可以与伯氏疏螺旋体结合并促进伯氏疏螺旋体从蜱虫肠道迁移。关键信息：伯氏疏螺旋体利用蜱虫蛋白来协调其向宿主的传播。伯氏疏螺旋体能够与肩突硬蜱营养不良聚糖样蛋白（ISDLP）结合。抑制蜱虫中的ISDLP会导致伯氏疏螺旋体向小鼠的传播减少。ISDLP是预防莱姆病的潜在靶点。
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