{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T14:43:18Z","timestamp":1792852998567,"version":"4.5.0"},"reference-count":108,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Syphilis, caused by <jats:italic>Treponema pallidum<\/jats:italic> subsp. <jats:italic>pallidum<\/jats:italic>, is an urgent global public health threat. Syphilis vaccine development has been impeded by limited understanding of the molecular mechanisms that enable <jats:italic>T. pallidum<\/jats:italic> to establish and maintain infection. The vascular endothelium is critical for <jats:italic>T. pallidum<\/jats:italic> attachment, dissemination, and host immune response initiation; however, the molecular details of <jats:italic>T. pallidum<\/jats:italic>-endothelial interactions are incompletely understood. To enhance understanding, we performed time-course transcriptomic profiling on <jats:italic>T. pallidum<\/jats:italic>-exposed brain microvascular endothelial cells. These analyses showed <jats:italic>T. pallidum<\/jats:italic> 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. In cells exposed to <jats:italic>T. pallidum<\/jats:italic>, the primary transcription factor associated with this process (Snail) was increased at both the transcript and protein levels, and microscopy analyses demonstrate F-actin cellular contraction. This study provides a comprehensive understanding of the molecular responses of endothelial cells to <jats:italic>T. pallidum<\/jats:italic> and identified the host pathways that might cause syphilis disease symptoms, information that could aid in syphilis vaccine design.<\/jats:p>","DOI":"10.3389\/fmicb.2025.1649738","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T05:22:33Z","timestamp":1759728153000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Time-course transcriptomics reveals the impact of Treponema pallidum on microvascular endothelial cell function and phenotype"],"prefix":"10.3389","volume":"16","author":[{"given":"Sean","family":"Waugh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara C.","family":"Goodyear","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alloysius","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Ranasinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen V.","family":"Lithgow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Falsafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E. 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