{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T18:03:10Z","timestamp":1772215390981,"version":"3.50.1"},"reference-count":76,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["18POST33990330"],"award-info":[{"award-number":["18POST33990330"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM127029"],"award-info":[{"award-number":["R35 GM127029"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013479","name":"Bay Area Lyme Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007864","name":"Brandeis University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    The spirochete\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    , which causes Lyme disease, has the most segmented genome among known bacteria. In addition to a linear chromosome, the\n                    <jats:italic>B<\/jats:italic>\n                    .\n                    <jats:italic>burgdorferi<\/jats:italic>\n                    genome contains over 20 linear and circular endogenous plasmids. While many of these plasmids are dispensable under in vitro culture conditions, they are maintained during the natural life cycle of the pathogen. Plasmid-encoded functions are required for colonization of the tick vector, transmission to the vertebrate host, and evasion of host immune defenses. Different\n                    <jats:italic>Borrelia<\/jats:italic>\n                    strains can vary substantially in the type of plasmids they carry. The gene composition within the same type of plasmid can also differ from strain to strain, impeding the inference of plasmid function from one strain to another. To facilitate the investigation of the role of specific\n                    <jats:italic>B<\/jats:italic>\n                    .\n                    <jats:italic>burgdorferi<\/jats:italic>\n                    plasmids, we developed a Cas9-based approach that targets a plasmid for removal. As a proof-of-principle, we showed that targeting wild-type Cas9 to several loci on the endogenous plasmids lp25 or lp28-1 of the\n                    <jats:italic>B<\/jats:italic>\n                    .\n                    <jats:italic>burgdorferi<\/jats:italic>\n                    type strain B31 results in sgRNA-specific plasmid loss even when homologous sequences (i.e., potential sequence donors for DNA recombination) are present nearby. Cas9 nickase versions, Cas9\n                    <jats:sup>D10A<\/jats:sup>\n                    or Cas9\n                    <jats:sup>H840A<\/jats:sup>\n                    , also cause plasmid loss, though not as robustly. Thus, sgRNA-directed Cas9 DNA cleavage provides a highly efficient way to eliminate\n                    <jats:italic>B<\/jats:italic>\n                    .\n                    <jats:italic>burgdorferi<\/jats:italic>\n                    endogenous plasmids that are non-essential in axenic culture.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0278151","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T13:45:08Z","timestamp":1669643108000},"page":"e0278151","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cas9-mediated endogenous plasmid loss in Borrelia burgdorferi"],"prefix":"10.1371","volume":"17","author":[{"given":"Constantin N.","family":"Takacs","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James E.","family":"Haber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0980-5334","authenticated-orcid":true,"given":"Christine","family":"Jacobs-Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"issue":"2","key":"pone.0278151.ref001","doi-asserted-by":"crossref","first-page":"616","DOI":"10.3201\/eid2702.202731","article-title":"Estimating the frequency of Lyme disease diagnoses, United States, 2010\u20132018","volume":"27","author":"KJ Kugeler","year":"2021","journal-title":"Emerg Infect 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