{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:32:32Z","timestamp":1789623152131,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011259","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000}}],"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI144133"],"award-info":[{"award-number":["U19AI144133"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014895","name":"Open Philanthropy Project","doi-asserted-by":"publisher","award":["#8394150"],"award-info":[{"award-number":["#8394150"]}],"id":[{"id":"10.13039\/100014895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The TprK protein of the syphilis agent,\n                      <jats:italic>Treponema pallidum<\/jats:italic>\n                      subsp.\n                      <jats:italic>pallidum<\/jats:italic>\n                      (\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      ), undergoes antigenic variation in seven discrete variable (V) regions via non-reciprocal segmental gene conversion. These recombination events transfer information from a repertoire of 53 silent chromosomal donor cassettes (DCs) into the single\n                      <jats:italic>tprK<\/jats:italic>\n                      expression site to continually generate TprK variants. Several lines of research developed over the last two decades support the theory that this mechanism is central to\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      \u2019s ability for immune avoidance and persistence in the host. Structural and modeling data, for example, identify TprK as an integral outer membrane porin with the V regions exposed on the pathogen\u2019s surface. Furthermore, infection-induced antibodies preferentially target the V regions rather than the predicted \u03b2-barrel scaffolding, and sequence variation abrogates the binding of antibodies elicited by antigenically different V regions. Here, we engineered a\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      strain to impair its ability to vary TprK and assessed its virulence in the rabbit model of syphilis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Principal findings<\/jats:title>\n                    <jats:p>\n                      A suicide vector was transformed into the wild-type (WT) SS14\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      isolate to eliminate 96% of its\n                      <jats:italic>tprK<\/jats:italic>\n                      DCs. The resulting SS14-DC\n                      <jats:sup>KO<\/jats:sup>\n                      strain exhibited an\n                      <jats:italic>in vitro<\/jats:italic>\n                      growth rate identical to the untransformed strain, supporting that the elimination of the DCs did not affect strain viability in absence of immune pressure. In rabbits injected intradermally with the SS14-DC\n                      <jats:sup>KO<\/jats:sup>\n                      strain, generation of new TprK sequences was impaired, and the animals developed attenuated lesions with a significantly reduced treponemal burden compared to control animals. During infection, clearance of V region variants originally in the inoculum mirrored the generation of antibodies to these variants, although no new variants were generated in the SS14-DC\n                      <jats:sup>KO<\/jats:sup>\n                      strain to overcome immune pressure. Na\u00efve rabbits that received lymph node extracts from animals infected with the SS14-DC\n                      <jats:sup>KO<\/jats:sup>\n                      strain remained uninfected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These data further support the critical role of TprK in\n                      <jats:italic>T<\/jats:italic>\n                      .\n                      <jats:italic>pallidum<\/jats:italic>\n                      virulence and persistence during infection.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.ppat.1011259","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T13:27:52Z","timestamp":1679318872000},"page":"e1011259","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":31,"title":["Treponema pallidum subsp. pallidum with an Artificially impaired TprK antigenic variation system is attenuated in the Rabbit model of syphilis"],"prefix":"10.1371","volume":"19","author":[{"given":"Emily","family":"Romeis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A. 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