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The alternative sigma factor RpoS plays a central role in borrelial host adaptation. Global transcriptome analyses suggested that more than 100 genes might be regulated by RpoS, but the main part of the regulon remains unexplored. Here, we showed that the expression of\n              <jats:italic>bb0689<\/jats:italic>\n              , a gene encoding an outer surface lipoprotein with unknown function, was activated by RpoS. By analyzing gene expression using luciferase reporter assays and quantitative reverse transcription PCR, we found that expression of\n              <jats:italic>bb0689<\/jats:italic>\n              was induced by an elevated temperature, a reduced pH, and increased cell density during\n              <jats:italic>in vitro<\/jats:italic>\n              cultivation. The transcriptional start site and a functional promoter for gene expression were identified in the 5\u2032 regulatory region of\n              <jats:italic>bb0689<\/jats:italic>\n              . The promoter was responsive to environmental stimuli and influenced by RpoS. We also showed that\n              <jats:italic>bb0689<\/jats:italic>\n              expression was expressed in\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              during animal infection, suggesting the importance of this gene for infection. We further generated a\n              <jats:italic>bb0689<\/jats:italic>\n              mutant and found that the infectivity of the mutant was severely attenuated in a murine infection model. Although\n              <jats:italic>bb0689<\/jats:italic>\n              -deficient spirochetes exhibited no defect during\n              <jats:italic>in vitro<\/jats:italic>\n              growth, they were defective in resistance to osmotic stress.\n              <jats:italic>Cis<\/jats:italic>\n              -complementation of the mutant with a wild-type copy of\n              <jats:italic>bb0689<\/jats:italic>\n              fully rescued all phenotypes. Collectively, these results demonstrate that the RpoS-regulated gene\n              <jats:italic>bb0689<\/jats:italic>\n              is a key contributor to the optimal infection of\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              in animals.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/iai.00459-24","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T14:00:44Z","timestamp":1734357644000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>bb0689<\/i>\n            contributes to the virulence of\n            <i>Borrelia burgdorferi<\/i>\n            in a murine model of Lyme disease"],"prefix":"10.1128","volume":"93","author":[{"given":"Connor","family":"Waldron","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, University of South Florida","place":["Tampa, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sierra","family":"George","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of South Florida","place":["Tampa, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of South Florida","place":["Tampa, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Hsien","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of South Florida","place":["Tampa, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7427-1856","authenticated-orcid":true,"given":"Zhiming","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of South Florida","place":["Tampa, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1995.53.397"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.21775\/cimb.042.113"},{"key":"e_1_3_4_4_2","first-page":"167","article-title":"Ticks and Borrelia: model systems for investigating pathogen-arthropod interactions","volume":"5","author":"Schwan TG","year":"1996","unstructured":"Schwan TG. 1996. 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