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This pathogen can survive for at least 9 months in its tick vector in an apparent dormant state between blood meals, without losing cell proliferative capability when re-exposed to nutrients. Cultivated\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              cells grown to stationary phase or resuspended in nutrient-limited media are often used to study the effects of nutrient deprivation. However, a thorough assessment of the spirochete\u2019s ability to recover from nutrient depletion has been lacking. Our study shows that starved\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              cultures rapidly lose cell proliferative ability. Loss of genetic elements essential for cell proliferation contributes to the observed proliferative defect in stationary phase. The gradual decline in copies of genetic elements is not perfectly synchronized between chromosomes and plasmids, generating cells that harbor one or more copies of the essential chromosome but lack all copies of one or more non-essential plasmids. This phenomenon likely contributes to the well-documented issue of plasmid loss during\n              <jats:italic>in vitro<\/jats:italic>\n              cultivation of\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              . In contrast,\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              cells from ticks starved for 14 months showed no evidence of reduced cell proliferative ability or plasmid loss. Beyond their practical implications for studying\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              , these findings suggest that the midgut of the tick vector offers a unique environment that supports the maintenance of\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              \u2019s segmented genome and cell proliferative potential during periods of tick fasting.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                causes Lyme disease, a prevalent tick-borne illness.\n                <jats:italic>B. burgdorferi<\/jats:italic>\n                must survive long periods (months to a year) of apparent dormancy in the midgut of the tick vector between blood meals. Resilience to starvation is a common trait among bacteria. However, this study reveals that, in laboratory cultures,\n                <jats:italic>B. burgdorferi<\/jats:italic>\n                poorly endures starvation and rapidly loses viability. This decline is linked to a gradual loss of genetic elements required for cell proliferation. These results suggest that the persistence of\n                <jats:italic>B. burgdorferi<\/jats:italic>\n                in nature is likely shaped more by unique environmental conditions in the midgut of the tick vector than by an innate ability of this bacterium to endure nutrient deprivation.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jb.00457-24","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T14:00:11Z","timestamp":1739541611000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["<i>Borrelia burgdorferi<\/i>\n            loses essential genetic elements and cell proliferative potential during stationary phase in culture but not in the tick vector"],"prefix":"10.1128","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8949-6211","authenticated-orcid":false,"given":"Jessica","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biology, Stanford University","place":["Stanford, USA"]},{"name":"Sarafan ChEM-H Institute, Stanford University","place":["Stanford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4553-0668","authenticated-orcid":true,"given":"Constantin N.","family":"Takacs","sequence":"additional","affiliation":[{"name":"Sarafan ChEM-H Institute, Stanford University","place":["Stanford, USA"]},{"name":"Howard Hughes Medical Institute, Stanford University","place":["Stanford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua W.","family":"McCausland","sequence":"additional","affiliation":[{"name":"Sarafan ChEM-H Institute, Stanford University","place":["Stanford, USA"]},{"name":"Howard Hughes Medical Institute, Stanford University","place":["Stanford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Mueller","sequence":"additional","affiliation":[{"name":"Sarafan ChEM-H Institute, Stanford University","place":["Stanford, USA"]},{"name":"Howard Hughes Medical Institute, Stanford University","place":["Stanford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeline","family":"Buron","sequence":"additional","affiliation":[{"name":"Sarafan ChEM-H Institute, Stanford University","place":["Stanford, USA"]},{"name":"Howard Hughes Medical Institute, Stanford University","place":["Stanford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yashna","family":"Thappeta","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University","place":["Stanford, USA"]},{"name":"Sarafan ChEM-H Institute, Stanford University","place":["Stanford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Wachter","sequence":"additional","affiliation":[{"name":"National Institutes of Health, Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases","place":["Hamilton, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9489-3406","authenticated-orcid":true,"given":"Patricia A.","family":"Rosa","sequence":"additional","affiliation":[{"name":"National Institutes of Health, Laboratory of Bacteriology, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases","place":["Hamilton, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0980-5334","authenticated-orcid":true,"given":"Christine","family":"Jacobs-Wagner","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University","place":["Stanford, USA"]},{"name":"Sarafan ChEM-H Institute, Stanford University","place":["Stanford, USA"]},{"name":"Howard Hughes Medical Institute, Stanford University","place":["Stanford, USA"]},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine","place":["Stanford, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2015.02.010"},{"key":"e_1_3_4_3_2","volume-title":"Lyme disease and relapsing fever spirochetes: genomics, molecular biology, host interactions and disease pathogenesis","author":"Radolf JD","year":"2021","unstructured":"Radolf JD, Samuels DS. 2021. 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