{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:33:26Z","timestamp":1793277206308,"version":"4.5.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T00:00:00Z","timestamp":1793232000000},"content-version":"vor","delay-in-days":114,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000268","name":"RCUK | Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/010589"],"award-info":[{"award-number":["BB\/010589"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-051483"],"award-info":[{"award-number":["INV-051483"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Treponema pallidum<\/jats:italic>\n                    subsp.\n                    <jats:italic>pallidum<\/jats:italic>\n                    , the causative agent of syphilis, remains difficult to study owing to long-standing limitations in in vitro cultivation. Although a rabbit epithelial cell co-culture system (Sf1Ep) enabled major advances, the absence of human cell-based models limits clinical relevance and mechanistic understanding of host\u2013pathogen interactions. Here, we established a co-culture system using human epithelial cell lines capable of supporting\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    growth in vitro. Six epithelial or epithelial-like cell lines from diverse tissues were evaluated under microaerophilic conditions using standard cultivation medium. CAL-39 (vulva) and HepG2 (liver) supported\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    survival, replication, characteristic growth behaviours, and long-term passage at levels comparable to Sf1Ep cells. Growth kinetics, attachment dynamics, and motility were quantified over extended culture. Using live-cell imaging, we defined two distinct host-cell interaction behaviours: surface-associated crawling and stable single-polar attachment. Both behaviours were observed across all tested cell lines but persisted only in those permissive for sustained growth. Together, our findings establish clinically relevant human epithelial co-culture models for\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    , provide new insights into host-cell-dependent growth and motility, and create a platform for mechanistic studies of syphilis pathogenesis and vaccine target discovery.\n                  <\/jats:p>","DOI":"10.1038\/s42003-026-10635-9","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T02:32:41Z","timestamp":1783391561000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A human epithelial co-culture system reveals distinct host cell interaction behaviours for Treponema pallidum"],"prefix":"10.1038","volume":"9","author":[{"given":"Katia","family":"Capuccini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divenita","family":"Govender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Goulding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6293-5264","authenticated-orcid":false,"given":"Cecilia","family":"Kyanya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9681-1956","authenticated-orcid":false,"given":"Shivani","family":"Pasricha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3889-7274","authenticated-orcid":false,"given":"Lorenzo","family":"Giacani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4432-8505","authenticated-orcid":false,"given":"Nicholas R.","family":"Thomson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2371-3161","authenticated-orcid":false,"given":"Linda","family":"Grillov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"10635_CR1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.2471\/BLT.12.107623","volume":"91","author":"GB Gomez","year":"2013","unstructured":"Gomez, G. B. et al. Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis. Bull. World Health Organ. 91, 217\u2013226 (2013).","journal-title":"Bull. World Health Organ."},{"key":"10635_CR2","unstructured":"World Health Organization. Implementing the global health sector strategies on HIV, viral hepatitis and sexually transmitted infections, 2022\u20132030 |report on progress and gaps 2024. https:\/\/www.who.int\/publications\/i\/item\/9789240094925."},{"key":"10635_CR3","doi-asserted-by":"publisher","first-page":"e01153","DOI":"10.1128\/mBio.01153-18","volume":"9","author":"DG Edmondson","year":"2018","unstructured":"Edmondson, D. G., Hu, B. & Norris, S. J. Long-term in vitro culture of the syphilis spirochete Treponema pallidum subsp. pallidum. mBio. 9, e01153\u201318 (2018).","journal-title":"mBio"},{"key":"10635_CR4","doi-asserted-by":"publisher","first-page":"e1009612","DOI":"10.1371\/journal.ppat.1009612","volume":"17","author":"E Romeis","year":"2021","unstructured":"Romeis, E. et al. Genetic engineering of Treponema pallidum subsp. pallidum, the Syphilis spirochete. PLoS Pathog. 17, e1009612 (2021).","journal-title":"PLoS Pathog."},{"key":"10635_CR5","doi-asserted-by":"publisher","first-page":"e994","DOI":"10.1016\/S2666-5247(23)00219-7","volume":"4","author":"LC Tantalo","year":"2023","unstructured":"Tantalo, L. C. et al. Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study.  Lancet Microbe 4, e994\u2013e1004 (2023).","journal-title":"Lancet Microbe"},{"key":"10635_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009949","volume":"17","author":"BDD Lay","year":"2021","unstructured":"Lay, B. D. D., Cameron, T. A., Lay, N. R. D., Norris, S. J. & Edmondson, D. G. Comparison of transcriptional profiles of Treponema pallidum during experimental infection of rabbits and in vitro culture: Highly similar, yet different. PLOS Pathog. 17, e1009949 (2021).","journal-title":"PLOS Pathog."},{"key":"10635_CR7","doi-asserted-by":"crossref","unstructured":"In-Depth Proteome Coverage of In Vitro-Cultured Treponema pallidum and Quantitative Comparison Analyses with In Vivo-Grown Treponemes. J. Proteome Res. 23, 1725\u20131743 (2024).","DOI":"10.1021\/acs.jproteome.3c00891"},{"key":"10635_CR8","doi-asserted-by":"publisher","first-page":"e44","DOI":"10.1002\/cpz1.44","volume":"1","author":"DG Edmondson","year":"2021","unstructured":"Edmondson, D. G. & Norris, S. J. In vitro cultivation of the Syphilis Spirochete Treponema pallidum. Curr. Protoc. 1, e44 (2021).","journal-title":"Curr. Protoc."},{"key":"10635_CR9","doi-asserted-by":"publisher","first-page":"e0210902","DOI":"10.1371\/journal.pone.0210902","volume":"14","author":"B Church","year":"2019","unstructured":"Church, B., Wall, E., Webb, J. R. & Cameron, C. E. Interaction of Treponema pallidum, the syphilis spirochete, with human platelets. PLoS One 14, e0210902 (2019).","journal-title":"PLoS One"},{"key":"10635_CR10","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1073\/pnas.1114362109","volume":"109","author":"MW Harman","year":"2012","unstructured":"Harman, M. W. et al. The heterogeneous motility of the Lyme disease spirochete in gelatin mimics dissemination through tissue. Proc. Natl. Acad. Sci. USA. 109, 3059\u20133064 (2012).","journal-title":"Proc. Natl. Acad. Sci. 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Parameters affecting continuous in vitro culture of Treponema pallidum Strains. mBio. 12, e03536-20 (2021).","DOI":"10.1128\/mBio.03536-20"},{"key":"10635_CR14","doi-asserted-by":"publisher","first-page":"157","DOI":"10.7705\/biomedica.6603","volume":"43","author":"D Trujillo","year":"2023","unstructured":"Trujillo, D. et al. Bone involvement in non-congenital syphilis. Biomedica 43, 157\u2013163 (2023).","journal-title":"Biomedica"},{"key":"10635_CR15","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.idcr.2018.03.015","volume":"12","author":"K Okamoto","year":"2018","unstructured":"Okamoto, K., Hatakeyama, S., Umezawa, M. & Hayashi, S. Gastric syphilis: the great imitator in the stomach. IDCases 12, 97\u201398 (2018).","journal-title":"IDCases"},{"key":"10635_CR16","doi-asserted-by":"crossref","unstructured":"Al Dallal, H. A. et al. Case report: Syphilitic Hepatitis\u2013a rare and underrecognized aetiology of liver disease with potential for misdiagnosis. Front. 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