{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T14:08:37Z","timestamp":1767708517012,"version":"3.48.0"},"posted":{"date-parts":[[2026,1,5]]},"group-title":"Microbiology","reference-count":82,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>Treponema pallidum<\/jats:italic>\n                  subspecies\n                  <jats:italic>pallidum<\/jats:italic>\n                  (\n                  <jats:italic>T. 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>\n                    <jats:underline>T<\/jats:underline>\n                    .\n                    <jats:underline>p<\/jats:underline>\n                    allidum\n                  <\/jats:italic>\n                  <jats:underline>r<\/jats:underline>\n                  epeat (Tpr) family of outer membrane proteins are immunogenic but have been implicated in immune evasion due to antigenic variation, indicating that Tprs are virulence factors displayed on the spirochetes surface. Long-term survival of\n                  <jats:italic>T. pallidum<\/jats:italic>\n                  is largely attributed to the sparse surface-exposed outer membrane proteins and antigenic variation exhibited by the major surface protein TprK, which undergoes phase variation. Mechanism of antigenic variation has been studied for decades; however, functions of Tprs in this extracellular pathogen have not been experimentally determined. In this study, we determined TprD and TprK location, their role in adherence and in clearance of\n                  <jats:italic>T. pallidum<\/jats:italic>\n                  by macrophages. Using our now established heterologous surrogate system and gain-in-function approach using non-adherent related spirochete, the B314 strain of\n                  <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                  , we show that both TprD and TprK are surface exposed to some extent on engineered\n                  <jats:italic>B. burgdorferi<\/jats:italic>\n                  as well as on\n                  <jats:italic>T. pallidum<\/jats:italic>\n                  Nichols and SS14 strains. We further demonstrate that both proteins mediate adherence to different mammalian cells\n                  <jats:italic>in vitro<\/jats:italic>\n                  and mouse antibodies generated against TprD and TprK putative surface loops bind spirochetes and promote J774A.1 macrophages-mediated opsonophagocytosis. Thus, surface-exposed adhesins TprD and TprK of\n                  <jats:italic>T. pallidum<\/jats:italic>\n                  contribute to binding to different types of cells which likely reflect the pathogen\u2019s ability to colonize different tissues, and they are also targets of opsonic antibodies.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>\n                    Syphilis remains a major global public health challenge and is exacerbated by the rising number of cases of congenital infection and increased risk of HIV acquisition and transmission in syphilitic patients. A critical barrier to improving understanding of the molecular basis of syphilis pathogenesis owe to fragility of\n                    <jats:italic>T. pallidum<\/jats:italic>\n                    , inability to grow it in pure culture, and difficulty in generating knockout mutants in predicted virulence factors due to their possible essential role in spirochetes viability. Our findings provide experimental evidence linking Tpr proteins to host cell adherence, their ability to generate humoral immune response in the rabbit model of infection as well as in humans which could facilitate clearance by macrophages. Demonstration of TprD and TprK as the targets of opsonic antibodies here highlight their potential as protective immunogens and emphasizes importance of their inclusion in the cocktail to produce effective vaccine against syphilis.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.04.697605","type":"posted-content","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T11:30:20Z","timestamp":1767612620000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Treponema pallidum<\/i>\n                  TprD and TprK Are Adhesins and Promote Spirochetes Opsonophagocytosis"],"prefix":"10.64898","author":[{"given":"Kashaf","family":"Zafar","sequence":"first","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics Rutgers-New Jersey Medical School, Newark, NJ 07103-3535"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Onyedikachi C.","family":"Azuama","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics Rutgers-New Jersey Medical School, Newark, NJ 07103-3535"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy & Infectious Diseases, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Giacani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy & Infectious Diseases, University of Washington, Seattle, WA, USA"},{"name":"Department of Global Health, University of Washington, Seattle, WA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0592-0693","authenticated-orcid":false,"given":"Nikhat","family":"Parveen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry and Molecular Genetics Rutgers-New Jersey Medical School, Newark, NJ 07103-3535"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"Suppl 1","key":"2026010606050508000_2026.01.04.697605v1.1","first-page":"S12","article-title":"Global prevalence and incidence estimates of selected curable STDs","volume":"74","year":"1998","journal-title":"Sexually transmitted infections"},{"key":"2026010606050508000_2026.01.04.697605v1.2","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.18.228486"},{"key":"2026010606050508000_2026.01.04.697605v1.3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011259"},{"key":"2026010606050508000_2026.01.04.697605v1.4","unstructured":"Organization WH . 2024. 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