{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T20:29:11Z","timestamp":1784147351583,"version":"3.55.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI083640"],"award-info":[{"award-number":["AI083640"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI152235"],"award-info":[{"award-number":["AI152235"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82072310"],"award-info":[{"award-number":["82072310"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2024,2,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Glycerol utilization as a carbohydrate source by\n              <jats:italic>Borreliella burgdorferi<\/jats:italic>\n              , the Lyme disease spirochete, is critical for its successful colonization and persistence in the tick vector. The expression of the\n              <jats:italic>glpFKD<\/jats:italic>\n              (\n              <jats:italic>glp<\/jats:italic>\n              ) operon, which encodes proteins for glycerol uptake\/utilization, must be tightly regulated during the enzootic cycle of\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              . Previous studies have established that the second messenger cyclic di-GMP (c-di-GMP) is required for the activation of\n              <jats:italic>glp<\/jats:italic>\n              expression, while an alternative sigma factor RpoS acts as a negative regulator for\n              <jats:italic>glp<\/jats:italic>\n              expression. In the present study, we report identification of a\n              <jats:italic>cis<\/jats:italic>\n              element within the 5\u00b4 untranslated region of\n              <jats:italic>glp<\/jats:italic>\n              that exerts negative regulation of\n              <jats:italic>glp<\/jats:italic>\n              expression. Further genetic screen of known and predicted DNA-binding proteins encoded in the genome of\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              uncovered that overexpressing\n              <jats:italic>Borrelia<\/jats:italic>\n              host adaptation regulator (BadR), a known global regulator, dramatically reduced\n              <jats:italic>glp<\/jats:italic>\n              expression. Similarly, the\n              <jats:italic>badR<\/jats:italic>\n              mutant significantly increased\n              <jats:italic>glp<\/jats:italic>\n              expression. Subsequent electrophoretic mobility shift assay analyses demonstrated that BadR directly binds to this\n              <jats:italic>cis<\/jats:italic>\n              element, thereby repressing\n              <jats:italic>glp<\/jats:italic>\n              independent of RpoS-mediated repression. The efficiency of BadR binding was further assessed in the presence of c-di-GMP and various carbohydrates. This finding highlights multi-layered positive and negative regulatory mechanisms employed by\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              to synchronize\n              <jats:italic>glp<\/jats:italic>\n              expression throughout its enzootic cycle.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              <jats:italic>Borreliella burgdorferi<\/jats:italic>\n              , the Lyme disease pathogen, must modulate its gene expression differentially to adapt successfully to its two disparate hosts. Previous studies have demonstrated that the glycerol uptake and utilization operon,\n              <jats:italic>glpFKD<\/jats:italic>\n              , plays a crucial role in spirochetal survival within ticks. However, the\n              <jats:italic>glpFKD<\/jats:italic>\n              expression must be repressed when\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              transitions to the mammalian host. In this study, we identified a specific\n              <jats:italic>cis<\/jats:italic>\n              element responsible for the repression of\n              <jats:italic>glpFKD<\/jats:italic>\n              . We further pinpointed\n              <jats:italic>Borrelia<\/jats:italic>\n              host adaptation regulator as the direct binding protein to this\n              <jats:italic>cis<\/jats:italic>\n              element, thereby repressing\n              <jats:italic>glpFKD<\/jats:italic>\n              expression. This discovery paves the way for a deeper exploration of how zoonotic pathogens sense distinct hosts and switch their carbon source utilization during transmission.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jb.00340-23","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T14:00:49Z","timestamp":1705068049000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["BadR directly represses the expression of the glycerol utilization operon in the Lyme disease pathogen"],"prefix":"10.1128","volume":"206","author":[{"given":"Jun-Jie","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4526-307X","authenticated-orcid":false,"given":"Sajith","family":"Raghunandanan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Wenzhou People\u2019s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9272-9207","authenticated-orcid":false,"given":"Raj","family":"Priya","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5328-6239","authenticated-orcid":true,"given":"Fuad","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"},{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Lou","sequence":"additional","affiliation":[{"name":"Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7231-3167","authenticated-orcid":false,"given":"X. Frank","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2714"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198303313081301"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-0400-5"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/37551"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.MBP-0011-2014"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01698.x"},{"key":"e_1_3_2_8_2","first-page":"103","volume-title":"Borrelia: molecular biology, host interaction and pathogenesis","author":"Gherardini F","year":"2010","unstructured":"Gherardini F, Boylan J, Lawence K, Skare J. 2010. Metabolism and physiology of Borrelia, p 103\u2013138. In Samules DS, Radolf JD (ed), Borrelia: molecular biology, host interaction and pathogenesis. Caister Academic Press, Norfolk, UK."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jmedent\/33.1.6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002102"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002133"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12609"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00315-15"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010385"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12882"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005242"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05136-11"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07687.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00243-18"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05860.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0118063"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06621.x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01238-13"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.21775\/cimb.042.223"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2023.102332"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231442498"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01204-17"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1180"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12171"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13206"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1099\/13500872-140-9-2349"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1184"},{"key":"e_1_3_2_33_2","first-page":"371","article-title":"Regulation of PTS gene expression by the homologous transcriptional regulators, Mlc and NagC, in Escherichia coli (or how two similar repressors can behave differently)","volume":"3","author":"Plumbridge J","year":"2001","unstructured":"Plumbridge J. 2001. Regulation of PTS gene expression by the homologous transcriptional regulators, Mlc and NagC, in Escherichia coli (or how two similar repressors can behave differently). J Mol Microbiol Biotechnol 3:371\u2013380.","journal-title":"J Mol Microbiol Biotechnol"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1669"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01476-10"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0203286"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00057-18"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00033-18"},{"key":"e_1_3_2_39_2","first-page":"521","article-title":"Isolation and cultivation of Lyme disease spirochetes","volume":"57","author":"Barbour AG","year":"1984","unstructured":"Barbour AG. 1984. Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med 57:521\u2013525.","journal-title":"Yale J Biol Med"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031960"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02454-06"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00253-12"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2008\/019992-0"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2011.05.004"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.249"}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jb.00340-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jb.00340-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T23:25:49Z","timestamp":1715815549000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jb.00340-23"}},"subtitle":[],"editor":[{"given":"Michael Y.","family":"Galperin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,22]]},"references-count":45,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,22]]}},"alternative-id":["10.1128\/jb.00340-23"],"URL":"https:\/\/doi.org\/10.1128\/jb.00340-23","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,22]]},"assertion":[{"value":"2023-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00340-23"}}