Time-course transcriptomics reveals the impact of Treponema pallidum on microvascular endothelial cell function and phenotype

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dc.contributor.authorWaugh, Sean
dc.contributor.authorGoodyear, Mara C.
dc.contributor.authorGomez, Alloysius
dc.contributor.authorRanasinghe, Akash
dc.contributor.authorLithgow, Karen V.
dc.contributor.authorFalsafi, Reza
dc.contributor.authorHancock, Robert E. W.
dc.contributor.authorLee, Amy H.
dc.contributor.authorCameron, Caroline E.
dc.date.accessioned2026-05-07T17:31:19Z
dc.date.available2026-05-07T17:31:19Z
dc.date.issued2025
dc.description.abstractSyphilis, caused by Treponema pallidum subsp. pallidum, is an urgent global public health threat. Syphilis vaccine development has been impeded by limited understanding of the molecular mechanisms that enable T. pallidum to establish and maintain infection. The vascular endothelium is critical for T. pallidum attachment, dissemination, and host immune response initiation; however, the molecular details of T. pallidum-endothelial interactions are incompletely understood. To enhance understanding, we performed time-course transcriptomic profiling on T. pallidum-exposed brain microvascular endothelial cells. These analyses showed T. pallidum 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 T. pallidum, 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 T. pallidum and identified the host pathways that might cause syphilis disease symptoms, information that could aid in syphilis vaccine design.
dc.description.reviewstatusReviewed
dc.description.scholarlevelFaculty
dc.description.sponsorshipThe author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by grants U19AI144133, U01AI18203 and the MERIT award R37AI051334 (CC) from the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH), as well as awards from Open Philanthropy (52345) and the Canadian Institutes for Health Research (CIHR; 506704 to CC and AL and 471857 to CC) and funding from CIHR Foundation grant FDN-154287 to RH. SW is the recipient of a CIHR Canada Graduate Scholarship-Doctoral (CGS-D), and MG is the recipient of a CIHR Postdoctoral Fellowship and a NIAID Developmental Research Project Award.
dc.identifier.citationWaugh, S., Goodyear, M. C., Gomez, A., Ranasinghe, A., Lithgow, K. V., Falsafi, R., Hancock, R. E. W., Lee, A. H., & Cameron, C. E. (2025b). Time-course transcriptomics reveals the impact of Treponema pallidum on microvascular endothelial cell function and phenotype. Frontiers in Microbiology, 16, 1649738. https://doi.org/10.3389/fmicb.2025.1649738
dc.identifier.urihttps://doi.org/10.3389/fmicb.2025.1649738
dc.identifier.urihttps://hdl.handle.net/1828/23851
dc.language.isoen
dc.publisherFrontiers in Microbiology
dc.rightsCC BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectsyphilis
dc.subjectvaccine
dc.subjecttranscriptomics
dc.subjectTreponema pallidum
dc.subjectendothelial cell
dc.subjectpathogenesis
dc.subjectSexual and Reproductive Health and Rights (SRHR) Aspiration Research Cluster
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.titleTime-course transcriptomics reveals the impact of Treponema pallidum on microvascular endothelial cell function and phenotype
dc.typeArticle

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