{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:32:22Z","timestamp":1793370742056,"version":"4.5.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["ZIA DE000751"],"award-info":[{"award-number":["ZIA DE000751"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI45801"],"award-info":[{"award-number":["AI45801"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI080615, AI116620"],"award-info":[{"award-number":["AI080615, AI116620"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,4,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The segmented genome of\n                      <jats:italic toggle=\"yes\">Borrelia burgdorferi<\/jats:italic>\n                      , the tick-borne agent of Lyme disease, encodes numerous chromosomal and plasmid-borne proteins and small RNAs (sRNAs) of unknown function that are critical for infectivity. Two recent examples are the linear plasmid (lp)17-encoded protein BBD18 and sRNA\n                      <jats:italic toggle=\"yes\">SR0736<\/jats:italic>\n                      (also termed as\n                      <jats:italic toggle=\"yes\">ittA<\/jats:italic>\n                      ), which promote spirochete survival in ticks and mammals, respectively. Using targeted mutagenesis of the\n                      <jats:italic toggle=\"yes\">bbd18<\/jats:italic>\n                      locus, complementation, and phenotypic analysis of isogenic mutants, we herein confirm and extend the regulatory roles of BBD18 and\n                      <jats:italic toggle=\"yes\">SR0736<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">ittA<\/jats:italic>\n                      ). A mutant lacking BBD18 and\n                      <jats:italic toggle=\"yes\">SR0736<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">ittA<\/jats:italic>\n                      ) persisted in ticks, yet failed to infect immunocompetent or immunodeficient mice. Although\n                      <jats:italic toggle=\"yes\">bbd18<\/jats:italic>\n                      complementation selectively restored\n                      <jats:italic toggle=\"yes\">bbd18<\/jats:italic>\n                      expression, it did not rescue murine infectivity, supporting an essential role for\n                      <jats:italic toggle=\"yes\">SR0736<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">ittA<\/jats:italic>\n                      ) during mammalian infection. Transcriptomic and proteomic analyses revealed widespread alterations in expression profiles that were only partially rescued by\n                      <jats:italic toggle=\"yes\">bbd18<\/jats:italic>\n                      complementation, suggesting distinct regulatory functions for BBD18 and\n                      <jats:italic toggle=\"yes\">SR0736<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">ittA<\/jats:italic>\n                      ). Because an additional sRNA (\n                      <jats:italic toggle=\"yes\">SR0735<\/jats:italic>\n                      ) lies immediately downstream relative to\n                      <jats:italic toggle=\"yes\">bbd18<\/jats:italic>\n                      , we generated an isogenic\n                      <jats:italic toggle=\"yes\">SR0735<\/jats:italic>\n                      inactivation mutant, which was likewise largely noninfectious in mice and exhibited dysregulation of multiple gene products, including the induction of several\n                      <jats:italic toggle=\"yes\">lp17<\/jats:italic>\n                      genes, such as\n                      <jats:italic toggle=\"yes\">bbd18<\/jats:italic>\n                      , and the downregulation of multiple proteins, such as OspC, BamA, and DbpA. Together, these data indicate that the\n                      <jats:italic toggle=\"yes\">bbd18<\/jats:italic>\n                      locus is surrounded by two essential sRNA elements,\n                      <jats:italic toggle=\"yes\">SR0735<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">SR0736<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">ittA<\/jats:italic>\n                      ), all three of which independently regulate genes, including ones impacting mammalian infectivity. Further characterization of such atypical regulatory elements in\n                      <jats:italic toggle=\"yes\">B. burgdorferi<\/jats:italic>\n                      may inform new control strategies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Borrelia burgdorferi<\/jats:italic>\n                      , the tick-borne agent of Lyme disease, is the causative agent of one of the most prevalent vector-borne infections in many regions worldwide. Despite extensive study, the biological functions of many of its protein and small RNA (sRNA) products remain poorly defined. Here, we confirm and extend the regulatory roles of the linear plasmid (\n                      <jats:italic toggle=\"yes\">lp<\/jats:italic>\n                      )17-encoded protein BBD18 and the sRNA\n                      <jats:italic toggle=\"yes\">SR0736<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">ittA<\/jats:italic>\n                      ) in spirochete infectivity. Importantly, we identify a previously unrecognized regulatory function for an adjacent sRNA,\n                      <jats:italic toggle=\"yes\">SR0735<\/jats:italic>\n                      , underscoring lp17 as a key regulatory region in\n                      <jats:italic toggle=\"yes\">B. burgdorferi<\/jats:italic>\n                      . Together, our findings highlight the\n                      <jats:italic toggle=\"yes\">bbd18<\/jats:italic>\n                      locus and its surrounding sRNA elements as an independent, multilayered regulatory module that controls gene products, including those required for mammalian infection. Defining how these three regulators shape gene expression and virulence will reveal new mechanisms underlying Lyme disease pathogenesis and may inform the development of new strategies to prevent this widespread illness.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00024-26","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T14:21:27Z","timestamp":1772461287000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["The\n                    <i>lp17<\/i>\n                    regulatory elements in\n                    <i>Borrelia burgdorferi<\/i>\n                    : a novel small RNA impacts gene expression and mammalian infection"],"prefix":"10.1128","volume":"17","author":[{"given":"Chrysoula","family":"Kitsou","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland","place":["College Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith","family":"Kung","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland","place":["College Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamoltip","family":"Promnares","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland","place":["College Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7997-5676","authenticated-orcid":true,"given":"Manish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland","place":["College Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7641-7350","authenticated-orcid":true,"given":"Ozlem B.","family":"Yas","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Veterinary Medicine, Ondokuz Mayis University","place":["Samsun, Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/004a2wv92","id-type":"ROR","asserted-by":"publisher"}],"name":"Mass Spectrometry Facility, National Institute of Dental and Craniofacial Research, National Institutes of Health","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radha","family":"Iyer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dkvy735","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Microbiology & Immunology, New York Medical College","place":["Valhalla, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8373-2159","authenticated-orcid":true,"given":"Ira","family":"Schwartz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03dkvy735","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Microbiology & Immunology, New York Medical College","place":["Valhalla, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7504-4628","authenticated-orcid":true,"given":"Utpal","family":"Pal","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland","place":["College Park, USA"]},{"name":"Virginia Maryland College of Veterinary Medicine","place":["College Park, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"CDC. 2021. How many people get Lyme disease? Available from: https:\/\/wwwcdcgov\/lyme\/data-research\/facts-stats\/indexhtml"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00018-19"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz872"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.1127"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2022.10.006"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/82_2017_51"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12816"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.21775\/cimb.042.113"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.21775\/cimb.042.223"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2023.102332"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07687.x"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01923"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093141"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01017-14"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009072"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008423"},{"key":"e_1_3_5_18_2","first-page":"317","article-title":"Small RNAs of Borrelia burgdorferi: characterizing functional regulators in a sea of sRNAs","volume":"90","author":"Lybecker MC","year":"2017","unstructured":"Lybecker MC, Samuels DS. 2017. Small RNAs of Borrelia burgdorferi: characterizing functional regulators in a sea of sRNAs. Yale J Biol Med 90:317\u2013323.","journal-title":"Yale J Biol Med"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39576-1"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01496-10"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35897-3"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000326"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/microarrays5020009"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.15.4572-4582.1994"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7383-5_19"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7383-5_9"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.00024-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.00024-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T13:01:54Z","timestamp":1775653314000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.00024-26"}},"subtitle":[],"editor":[{"given":"Karine A.","family":"Gibbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,8]]}},"alternative-id":["10.1128\/mbio.00024-26"],"URL":"https:\/\/doi.org\/10.1128\/mbio.00024-26","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,8]]},"assertion":[{"value":"2026-01-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00024-26"}}