{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:12:41Z","timestamp":1785413561511,"version":"3.56.0"},"posted":{"date-parts":[[2025,5,6]]},"group-title":"Molecular Biology","reference-count":104,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health","award":["U19AI144133"],"award-info":[{"award-number":["U19AI144133"]}]},{"name":"National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health","award":["U01AI18203"],"award-info":[{"award-number":["U01AI18203"]}]},{"name":"National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health","award":["R37AI051334"],"award-info":[{"award-number":["R37AI051334"]}]},{"name":"Open Philanthropy","award":["52345"],"award-info":[{"award-number":["52345"]}]},{"award":["506704"],"award-info":[{"award-number":["506704"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"award":["471857"],"award-info":[{"award-number":["471857"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"award":["FDN-154287"],"award-info":[{"award-number":["FDN-154287"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,5]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Syphilis, caused by\n                  <jats:italic>Treponema pallidum<\/jats:italic>\n                  subsp.\n                  <jats:italic>pallidum,<\/jats:italic>\n                  is an urgent global public health threat. Syphilis vaccine development has been impeded by limited understanding of the molecular mechanisms that enable\n                  <jats:italic>T. pallidum<\/jats:italic>\n                  to establish and maintain infection. The vascular endothelium is critical for\n                  <jats:italic>T. pallidum<\/jats:italic>\n                  attachment, dissemination, and host immune response initiation; however, the molecular details of\n                  <jats:italic>T. pallidum<\/jats:italic>\n                  -endothelial interactions are incompletely understood. To enhance understanding, we performed time-course transcriptomic profiling on\n                  <jats:italic>T. pallidum<\/jats:italic>\n                  -exposed brain microvascular endothelial cells. These analyses showed\n                  <jats:italic>T. pallidum<\/jats:italic>\n                  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\n                  <jats:italic>T. pallidum<\/jats:italic>\n                  and identified the host pathways that might cause syphilis disease symptoms, information that could aid in syphilis vaccine design.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"simple\">\n                    <jats:list-item>\n                      <jats:p>\n                        \u25a1 Exposure of microvascular endothelial cells to\n                        <jats:italic>Treponema pallidum<\/jats:italic>\n                        subsp.\n                        <jats:italic>Pallidum<\/jats:italic>\n                        significantly alters the endothelial cell transcriptome\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        \u25a1 Signaling pathways related to extracellular matrix organization, growth factors, integrins, and Rho GTPases were overrepresented for genes differentially expressed in\n                        <jats:italic>T. pallidum<\/jats:italic>\n                        -exposed endothelial cells\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        \u25a1 Exposure to\n                        <jats:italic>T. pallidum<\/jats:italic>\n                        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\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        \u25a1\n                        <jats:italic>T. pallidum<\/jats:italic>\n                        exposure induces expression of Snail, the main transcription factor associated with the process of endothelial to mesenchymal transition\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"651946v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.05.04.651946","type":"posted-content","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T03:55:22Z","timestamp":1746590122000},"source":"Crossref","is-referenced-by-count":0,"title":["Time-course Transcriptomics Reveals the Impact of\n                  <i>Treponema pallidum<\/i>\n                  on Microvascular Endothelial Cell Function and Phenotype"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1154-1850","authenticated-orcid":false,"given":"Sean","family":"Waugh","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Microbiology, University of Victoria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7509-7375","authenticated-orcid":false,"given":"Mara C.","family":"Goodyear","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, University of Victoria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alloysius","family":"Gomez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, University of 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