Time-course Transcriptomics Reveals the Impact of on Microvascular Endothelial Cell Function and Phenotype.

UNLABELLED

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.

HIGHLIGHTS

□ 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.