Waugh Sean, Goodyear Mara C, Gomez Alloysius, Ranasinghe Akash, Lithgow Karen V, Falsafi Reza, Hancock Robert E W, Lee Amy H, Cameron Caroline E
bioRxiv. 2025 May 5:2025.05.04.651946. doi: 10.1101/2025.05.04.651946.
Syphilis, caused by subsp. is an urgent global public health threat. Syphilis vaccine development has been impeded by limited understanding of the molecular mechanisms that enable to establish and maintain infection. The vascular endothelium is critical for attachment, dissemination, and host immune response initiation; however, the molecular details of -endothelial interactions are incompletely understood. To enhance understanding, we performed time-course transcriptomic profiling on -exposed brain microvascular endothelial cells. These analyses showed exposure altered pathways related to extracellular matrix, growth factors, integrins, and Rho GTPases. The induced transcriptional response was consistent with endothelial to mesenchymal transition, a process involved in fetal development and vascular dysfunction. This study provides a comprehensive understanding of the molecular responses of endothelial cells to and identified the host pathways that might cause syphilis disease symptoms, information that could aid in syphilis vaccine design.
□ Exposure of microvascular endothelial cells to subsp. significantly alters the endothelial cell transcriptome □ Signaling pathways related to extracellular matrix organization, growth factors, integrins, and Rho GTPases were overrepresented for genes differentially expressed in -exposed endothelial cells □ Exposure to induces pathways and factors consistent with endothelial to mesenchymal transition, a host process central to development that may explain the devastating effects of congenital infection □ exposure induces expression of Snail, the main transcription factor associated with the process of endothelial to mesenchymal transition.
由苍白密螺旋体亚种引起的梅毒是一项紧迫的全球公共卫生威胁。梅毒疫苗的研发因对梅毒螺旋体建立和维持感染的分子机制了解有限而受阻。血管内皮对于梅毒螺旋体的附着、传播及宿主免疫反应的启动至关重要；然而，梅毒螺旋体与内皮相互作用的分子细节仍未完全明了。为增进了解，我们对暴露于梅毒螺旋体的脑微血管内皮细胞进行了时间进程转录组分析。这些分析表明，梅毒螺旋体暴露改变了与细胞外基质、生长因子、整合素和Rho GTP酶相关的信号通路。诱导的转录反应与内皮向间充质转化一致，这一过程涉及胎儿发育和血管功能障碍。本研究全面了解了内皮细胞对梅毒螺旋体的分子反应，并确定了可能导致梅毒疾病症状的宿主信号通路，这些信息有助于梅毒疫苗的设计。
□ 微血管内皮细胞暴露于苍白密螺旋体亚种会显著改变内皮细胞转录组 □ 与细胞外基质组织、生长因子、整合素和Rho GTP酶相关的信号通路在暴露于梅毒螺旋体的内皮细胞中差异表达的基因中占比过高 □ 暴露于梅毒螺旋体诱导的信号通路和因子与内皮向间充质转化一致，这是发育过程中的一个关键宿主过程，可能解释先天性感染的毁灭性影响 □ 梅毒螺旋体暴露诱导Snail表达，Snail是与内皮向间充质转化过程相关的主要转录因子
