{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:21:03Z","timestamp":1785817263624,"version":"3.56.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0012348","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000}}],"reference-count":111,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"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":["R03AI151432"],"award-info":[{"award-number":["R03AI151432"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM103625"],"award-info":[{"award-number":["P20GM103625"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30GM145393"],"award-info":[{"award-number":["P30GM145393"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006295","name":"Office of the Vice Chancellor for Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006295","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008231","name":"Arkansas Biosciences Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008231","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><jats:underline>R<\/jats:underline>elapsing <jats:underline>f<\/jats:underline>ever (RF), a vector-borne disease caused by <jats:italic>Borrelia<\/jats:italic> spp., is characterized by recurring febrile episodes due to repeated bouts of bacteremia. RF spirochetes can be geographically and phylogenetically divided into two distinct groups; Old World RF <jats:italic>Borrelia<\/jats:italic> (found in Africa, Asia, and Europe) and New World RF <jats:italic>Borrelia<\/jats:italic> (found in the Americas). While RF is a rarely reported disease in the Americas, RF is prevalent in endemic parts of Africa. Despite phylogenetic differences between Old World and New World RF <jats:italic>Borrelia<\/jats:italic> and higher incidence of disease associated with Old World RF spirochete infection, genetic manipulation has only been described in New World RF bacteria. Herein, we report the generation of genetic tools for use in the Old World RF spirochete, <jats:italic>Borrelia duttonii<\/jats:italic>. We describe methods for transformation and establish shuttle vector- and integration-based approaches for genetic complementation, creating green fluorescent protein (<jats:italic>gfp<\/jats:italic>)-expressing <jats:italic>B<\/jats:italic>. <jats:italic>duttonii<\/jats:italic> strains as a proof of principle. Allelic exchange mutagenesis was also used to inactivate a homolog of the <jats:italic>Borrelia burgdorferi p66<\/jats:italic> gene, which encodes an important virulence factor, in <jats:italic>B<\/jats:italic>. <jats:italic>duttonii<\/jats:italic> and demonstrate that this mutant was attenuated in a murine model of RF. Finally, the <jats:italic>B<\/jats:italic>. <jats:italic>duttonii p66<\/jats:italic> mutant was complemented using shuttle vector- and <jats:italic>cis<\/jats:italic> integration-based approaches. As expected, complemented <jats:italic>p66<\/jats:italic> mutant strains were fully infectious, confirming that P66 is required for optimal mammalian infection. The genetic tools and techniques reported herein represent an important advancement in the study of RF <jats:italic>Borrelia<\/jats:italic> that allows for future characterization of virulence determinants and colonization factors important for the enzootic cycle of Old World RF spirochetes.<\/jats:p>","DOI":"10.1371\/journal.pntd.0012348","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T17:55:22Z","timestamp":1721670922000},"page":"e0012348","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development and validation of systems for genetic manipulation of the Old World tick-borne relapsing fever spirochete, Borrelia duttonii"],"prefix":"10.1371","volume":"18","author":[{"given":"Clay D.","family":"Jackson-Litteken","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanfeng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon A.","family":"Hogland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Tyler","family":"Ratliff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LeAnn","family":"McFadden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa S.","family":"Fullerton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Voth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan O. 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