{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:00:21Z","timestamp":1753880421903,"version":"3.41.2"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"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":["R01AI080615"],"award-info":[{"award-number":["R01AI080615"]}],"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":["P01AI138949"],"award-info":[{"award-number":["P01AI138949"]}],"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":["R01AI116620"],"award-info":[{"award-number":["R01AI116620"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"HHS | NIH | National Center for Advancing Translational Sciences","award":["ZIA TR000355-04"],"award-info":[{"award-number":["ZIA TR000355-04"]}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI029735-30"],"award-info":[{"award-number":["R01AI029735-30"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2023,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Borrelia burgdorferi,<\/jats:italic>\n            the pathogen of Lyme disease, encodes many conserved proteins of unknown structure or function, including ones that serve essential roles in microbial infectivity. One such protein is BB0238, which folds into a two-domain protein, as we have determined by X-ray crystallography and AlphaFold analysis. The N-terminal domain begins with a helix-turn-helix motif (HTH), previously referred to as a tetratricopeptide repeat (TPR) motif, known to mediate protein-protein interactions. The fold of the C-terminal domain has been seen in proteins with a range of unrelated activities and thus does not infer function. In addition to its previously known binding partner BB0323, another essential borrelial virulence determinant, we show that BB0238 also binds a second protein, BB0108, a borrelial ortholog of the chaperone protein SurA and the peptidyl-prolyl\n            <jats:italic>cis<\/jats:italic>\n            \/\n            <jats:italic>trans<\/jats:italic>\n            isomerase protein PrsA. An\n            <jats:italic>in vitro<\/jats:italic>\n            enzymatic assay confirmed the catalytic activity. We also determined the crystal structure of the catalytic domain of BB0108, which revealed the parvulin-type organization of the key catalytic residues. We show that BB0238 influences the proteolytic processing of BB0323, although the TPR\/HTH motif is not involved in the process. Instead, we show that the motif stabilizes BB0238 in the host environment and facilitates tick-to-mouse pathogen transmission by aiding spirochete evasion of early host cellular immunity. Taken together, these studies highlight the biological significance of BB0238 and its interactions with multiple\n            <jats:italic>B. burgdorferi<\/jats:italic>\n            proteins essential for microbial infection.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Lyme disease is a major tick-borne infection caused by a bacterial pathogen called\n              <jats:italic>Borrelia burgdorferi<\/jats:italic>\n              , which is transmitted by ticks and affects hundreds of thousands of people every year. These bacterial pathogens are distinct from other genera of microbes because of their distinct features and ability to transmit a multi-system infection to a range of vertebrates, including humans. Progress in understanding the infection biology of Lyme disease, and thus advancements towards its prevention, are hindered by an incomplete understanding of the microbiology of\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              , partly due to the occurrence of many unique borrelial proteins that are structurally unrelated to proteins of known functions yet are indispensable for pathogen survival. We herein report the use of diverse technologies to examine the structure and function of a unique\n              <jats:italic>B. burgdorferi<\/jats:italic>\n              protein, annotated as BB0238\u2014an essential virulence determinant. We show that the protein is structurally organized into two distinct domains, is involved in multiplex protein-protein interactions, and facilitates tick-to-mouse pathogen transmission by aiding microbial evasion of early host cellular immunity. We believe that our findings will further enrich our understanding of the microbiology of\n              <jats:italic>B. burgdorferi,<\/jats:italic>\n              potentially impacting the future development of novel prevention strategies against a widespread tick-transmitted infection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.02135-23","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T13:01:36Z","timestamp":1697202096000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["A unique borrelial protein facilitates microbial immune evasion"],"prefix":"10.1128","volume":"14","author":[{"given":"Shelby D.","family":"Foor","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland , College Park, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalvis","family":"Brangulis","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre , Riga, Latvia"},{"name":"Department of Human Physiology and Biochemistry, Riga Stradins University , Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil K.","family":"Shakya","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland , Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vipin S.","family":"Rana","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland , College Park, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandhya","family":"Bista","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland , College Park, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chrysoula","family":"Kitsou","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland , College Park, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Ronzetti","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland , College Park, Maryland, USA"},{"name":"National Center for Advancing Translational Sciences, National Institutes of Health , Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adit B.","family":"Alreja","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland , Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara B.","family":"Linden","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland , Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda S.","family":"Altieri","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland , Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bolormaa","family":"Baljinnyam","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences, National Institutes of Health , Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inara","family":"Akopjana","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre , Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3248-4831","authenticated-orcid":true,"given":"Daniel C.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland , College Park, Maryland, USA"},{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland , Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Simeonov","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences, National Institutes of Health , Rockville, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2823-7627","authenticated-orcid":true,"given":"Osnat","family":"Herzberg","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland , Rockville, Maryland, USA"},{"name":"Department of Chemistry and Biochemistry, University of Maryland , College Park, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1170-4102","authenticated-orcid":true,"given":"Melissa J.","family":"Caimano","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Pediatrics, and Molecular Biology and Biophysics, UConn Health , Farmington, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 , College Park, Maryland, USA"},{"name":"Virginia-Maryland College of Veterinary Medicine , College Park, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.48"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.21775\/cimb.042.097"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2714"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2015.02.010"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2708.204763"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.90"},{"key":"e_1_3_5_8_2","first-page":"467","volume-title":"Borrelia, molecular biology, host interaction and pathogenesis","author":"Marconi RT","year":"2010","unstructured":"Marconi RT , Earnhart CG . 2010. Lyme disease vaccines, p 467\u2013486. In Samuels DS , JD Radolf (ed), Borrelia, molecular biology, host interaction and pathogenesis. Caister Academic Press, Norfolk, UK."},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz872"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2013.01.008"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.121"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033280"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01158-10"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/37551"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00606-21"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/605846"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.70.10.5973-5979.2004"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00059-22"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12202"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03279-7"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12213"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu460"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01977-14"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00360-16"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3065"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798319010751"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2014.03.011"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018259"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-2"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa937"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa913"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80691-1"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2003.10.007"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsre.2004.12.008"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2010.10.009"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0969-2126(02)00877-8"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.622910"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0968-0004(00)89105-7"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.10.078"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi800964q"},{"key":"e_1_3_5_42_2","first-page":"1101","article-title":"Determination of enzymatic catalysis for the cis-trans-isomerization of peptide binding in proline-containing peptides","volume":"43","author":"Fischer G","year":"1984","unstructured":"Fischer G , Bang H , Mech C . 1984. Determination of enzymatic catalysis for the cis-trans-isomerization of peptide binding in proline-containing peptides. Biomed Biochim Acta 43:1101\u20131111.","journal-title":"Biomed Biochim Acta"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.3791\/2544"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis930"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2325"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780471729259.mc12c03s00"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn326"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200508166"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.31324"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13594"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2015.09.007"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1718595115"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1107\/S090744491003982X"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1107\/S160057751601403X"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910045749"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0108767307043930"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0350503"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444906022116"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444996012255"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(97)76066-X"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444903028956"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444912001308"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01488-1"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty1057"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi0313s48"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06853.x"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl3837"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.02135-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.02135-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,11]],"date-time":"2024-08-11T18:30:31Z","timestamp":1723401031000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.02135-23"}},"subtitle":[],"editor":[{"given":"Victor J.","family":"Torres","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":68,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,10,31]]}},"alternative-id":["10.1128\/mbio.02135-23"],"URL":"https:\/\/doi.org\/10.1128\/mbio.02135-23","relation":{},"ISSN":["2150-7511"],"issn-type":[{"type":"electronic","value":"2150-7511"}],"subject":[],"published":{"date-parts":[[2023,10,31]]},"assertion":[{"value":"2023-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02135-23"}}