{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:33:01Z","timestamp":1789623181482,"version":"build-2803163510"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Treponema pallidum<\/jats:italic>\n                      subspecies\n                      <jats:italic>pallidum<\/jats:italic>\n                      causes systemic syphilis, exclusively infects humans in nature and can persist for decades in the absence of treatment despite generating robust adaptive immune responses. The\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      repeat (Tpr) family of outer membrane proteins are immunogenic and are implicated in immune evasion, indicating them to be virulence factors displayed on the spirochete surface. Long-term survival of\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      is largely attributed to sparse surface-exposed outer membrane proteins and antigenic variation in the major surface protein TprK through phase variation. This mechanism has been studied for decades; however, the functions of Tprs of this extracellular pathogen are not yet experimentally determined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, the localization and functional roles of TprD and TprK were investigated using a heterologous spirochete expression system and a gain-of-function approach by employing a non-infectious, non-adherent\n                      <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                      B314 strain. Opsonophagocytosis of engineered\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      as well as of\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      Nichols and SS14 strains was evaluated using J774A.1 macrophages and mouse antibodies raised against predicted surface-exposed loops of TprD and TprK using IncuCyte system.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both TprD and TprK were found to be surface exposed in engineered\n                      <jats:italic>B. burgdorferi<\/jats:italic>\n                      and infectious\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      strains. Expression of these proteins conferred adherence to several mammalian cell lines\n                      <jats:italic>in vitro<\/jats:italic>\n                      . In addition, antibodies we generated recognized TprD and TprK on the surface of spirochetes and significantly enhanced macrophage-mediated opsonophagocytosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings here demonstrate that TprD and TprK function as\n                      <jats:italic>T. pallidum<\/jats:italic>\n                      adhesins that are also targets of opsonic antibodies. These Tprs likely facilitate tissue colonization during infection, while also rendering the pathogen susceptible to immune clearance. Our findings support inclusion of TprD and TprK as components of a multivalent vaccine against syphilis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1783902","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:30:49Z","timestamp":1772775049000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Treponema pallidum TprD and TprK are adhesins and their surface expression promotes spirochetal opsonophagocytosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Kashaf","family":"Zafar","sequence":"first","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School","place":["Newark, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onyedikachi C.","family":"Azuama","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School","place":["Newark, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda H.","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Allergy & Infectious Diseases, Department of Medicine, University of Washington","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Giacani","sequence":"additional","affiliation":[{"name":"Division of Allergy & Infectious Diseases, Department of Medicine, University of Washington","place":["Seattle, WA, United States"]},{"name":"Department of Global Health, University of Washington","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhat","family":"Parveen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School","place":["Newark, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"B1","article-title":"Global prevalence and incidence estimates of selected curable STDs","author":"Gerbase","year":"1998","journal-title":"Sexually Transmitted Infections"},{"key":"B2","doi-asserted-by":"publisher","first-page":"548","DOI":"10.2471\/BLT.18.228486","article-title":"Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016","volume":"97","author":"Rowley","year":"2019","journal-title":"Bull World Health Organ"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e1011259","DOI":"10.1371\/journal.ppat.1011259","article-title":"Treponema pallidum subsp. pallidum with an artificially impaired TprK antigenic variation system is attenuated in the rabbit model of syphilis","volume":"19","author":"Romeis","year":"2023","journal-title":"PloS Pathog"},{"key":"B4","volume-title":"Implementing the global health sector strategies on HIV, viral hepatitis and sexually transmitted infections, 2022\u20132030: report on progress and gaps 2024","year":"2024"},{"key":"B5","unstructured":"Syphilis\n          \n          2025"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.clindermatol.2023.12.002","article-title":"The global burden of sexually transmitted infections","volume":"42","author":"Sinka","year":"2024","journal-title":"Clinics Dermatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"5308","DOI":"10.3390\/jcm14155308","article-title":"The epidemiology of syphilis worldwide in the last decade","volume":"14","author":"Rosset","year":"2025","journal-title":"J Clin Med"},{"key":"B8","volume-title":"Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021: accountability for the global health sector strategies 2016\u20132021: actions for impact","year":"2021"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1448841","article-title":"Global, regional, and national burden of syphilis, 1990\u20132021 and predictions by Bayesian age-period-cohort analysis: a systematic analysis for the Global Burden of Disease Study 2021","volume":"11","author":"Yu","year":"2024","journal-title":"Front Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0146-0005(03)00006-5","article-title":"National institute of child health and human development maternal-fetal medicine units network. 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