{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:33:23Z","timestamp":1789475603818,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pntd.0009753","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000}}],"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI144133"],"award-info":[{"award-number":["U19AI144133"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI144133"],"award-info":[{"award-number":["U19AI144133"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Immune evasion by\n                    <jats:italic>Treponema pallidum<\/jats:italic>\n                    subspecies\n                    <jats:italic>pallidum<\/jats:italic>\n                    (\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>pallidum<\/jats:italic>\n                    ) has been attributed to antigenic variation of its putative outer-membrane protein TprK. In TprK, amino acid diversity is confined to seven variable (V) regions, and generation of sequence diversity within the V regions occurs via a non-reciprocal segmental gene conversion mechanism where donor cassettes recombine into the\n                    <jats:italic>tprK<\/jats:italic>\n                    expression site. Although previous studies have shown the significant role of immune selection in driving accumulation of TprK variants, the contribution of baseline gene conversion activity to variant diversity is less clear. Here, combining longitudinal\n                    <jats:italic>tprK<\/jats:italic>\n                    deep sequencing of near clonal Chicago C from immunocompetent and immunosuppressed rabbits along with the newly developed\n                    <jats:italic>in vitro<\/jats:italic>\n                    cultivation system for\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>pallidum<\/jats:italic>\n                    , we directly characterized TprK alleles in the presence and absence of immune selection. Our data confirm significantly greater sequence diversity over time within the V6 region during syphilis infection in immunocompetent rabbits compared to immunosuppressed rabbits, consistent with previous studies on the role of TprK in evasion of the host immune response. Compared to strains grown in immunocompetent rabbits, strains passaged\n                    <jats:italic>in vitro<\/jats:italic>\n                    displayed low level changes in allele frequencies of TprK variable region sequences similar to that of strains passaged in immunosuppressed rabbits. Notably, we found significantly increased rates of V6 allele generation relative to other variable regions in\n                    <jats:italic>in vitro<\/jats:italic>\n                    cultivated\n                    <jats:italic>T<\/jats:italic>\n                    ,\n                    <jats:italic>pallidum<\/jats:italic>\n                    strains, illustrating that the diversity within these hypervariable regions occurs in the complete absence of immune selection. Together, our results demonstrate antigenic variation in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>pallidum<\/jats:italic>\n                    can be studied\n                    <jats:italic>in vitro<\/jats:italic>\n                    and occurs even in the complete absence of immune pressure, allowing the\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>pallidum<\/jats:italic>\n                    population to continuously evade the immune system of the infected host.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0009753","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T13:55:53Z","timestamp":1631022953000},"page":"e0009753","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Longitudinal TprK profiling of in vivo and in vitro-propagated Treponema pallidum subsp. pallidum reveals accumulation of antigenic variants in absence of immune pressure"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6925-9948","authenticated-orcid":true,"given":"Michelle J.","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9122-9211","authenticated-orcid":true,"given":"Austin M.","family":"Haynes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Addetia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A. 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A.","family":"Lukehart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3889-7274","authenticated-orcid":true,"given":"Lorenzo","family":"Giacani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-0527","authenticated-orcid":true,"given":"Alexander L.","family":"Greninger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"pntd.0009753.ref001","volume-title":"Syphilis Surveillance Supplement 2013\u20132017","author":"Centers for Disease Control and Prevention","year":"2019"},{"key":"pntd.0009753.ref002","first-page":"402","article-title":"Primary and secondary syphilis\u2014United States, 2005\u20132013","volume":"63","author":"Centers for Disease Control and Prevention 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