{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:59:57Z","timestamp":1780383597028,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009869","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000}}],"reference-count":93,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI099094"],"award-info":[{"award-number":["R01AI099094"]}],"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":["R01AI059373"],"award-info":[{"award-number":["R01AI059373"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Research Fund for Tick-Borne Diseases"},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["FI2GM133345"],"award-info":[{"award-number":["FI2GM133345"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009633","name":"eunice kennedy shriver national institute of child health and human development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The Lyme disease spirochete <jats:italic>Borrelia burgdorferi<\/jats:italic> relies on uptake of essential nutrients from its host environments for survival and infection. Therefore, nutrient acquisition mechanisms constitute key virulence properties of the pathogen, yet these mechanisms remain largely unknown. <jats:italic>In vivo<\/jats:italic> expression technology applied to <jats:italic>B<\/jats:italic>. <jats:italic>burgdorferi<\/jats:italic> (BbIVET) during mammalian infection identified gene <jats:italic>bb0562<\/jats:italic>, which encodes a hypothetical protein comprised of a conserved domain of unknown function, DUF3996. DUF3996 is also found across adjacent encoded hypothetical proteins BB0563 and BB0564, suggesting the possibility that the three proteins could be functionally related. Deletion of <jats:italic>bb0562<\/jats:italic>, <jats:italic>bb0563<\/jats:italic> and <jats:italic>bb0564<\/jats:italic> individually and together demonstrated that <jats:italic>bb0562<\/jats:italic> alone was important for optimal disseminated infection in immunocompetent and immunocompromised mice by needle inoculation and tick bite transmission. Moreover, <jats:italic>bb0562<\/jats:italic> promoted spirochete survival during the blood dissemination phase of infection. Gene <jats:italic>bb0562<\/jats:italic> was also found to be important for spirochete growth in low serum media and the growth defect of \u0394<jats:italic>bb0562 B<\/jats:italic>. <jats:italic>burgdorferi<\/jats:italic> was rescued with the addition of various long chain fatty acids, particularly oleic acid. In mammals, fatty acids are primarily stored in fat droplets in the form of triglycerides. Strikingly, addition of glyceryl trioleate, the triglyceride form of oleic acid, to the low serum media did not rescue the growth defect of the mutant, suggesting <jats:italic>bb0562<\/jats:italic> may be important for the release of fatty acids from triglycerides. Therefore, we searched for and identified two canonical GXSXG lipase motifs within BB0562, despite the lack of homology to known bacterial lipases. Purified BB0562 demonstrated lipolytic activity dependent on the catalytic serine residues within the two motifs. In sum, we have established that <jats:italic>bb0562<\/jats:italic> is a novel nutritional virulence determinant, encoding a lipase that contributes to fatty acid scavenge for spirochete survival in environments deficient in free fatty acids including the mammalian host.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009869","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T18:37:55Z","timestamp":1629484675000},"page":"e1009869","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["BB0562 is a nutritional virulence determinant with lipase activity important for Borrelia burgdorferi infection and survival in fatty acid deficient environments"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7876-3521","authenticated-orcid":true,"given":"Hunter 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the dual-host lifestyle of Lyme disease spirochaetes","volume":"10","author":"JD Radolf","year":"2012","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"ppat.1009869.ref003","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.idc.2007.12.013","article-title":"Biology of infection with Borrelia burgdorferi","volume":"22","author":"K Tilly","year":"2008","journal-title":"Infect Dis Clin North Am"},{"issue":"9814","key":"ppat.1009869.ref004","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0140-6736(11)60103-7","article-title":"Lyme borreliosis","volume":"379","author":"G Stanek","year":"2012","journal-title":"Lancet"},{"key":"ppat.1009869.ref005","first-page":"114","article-title":"Borrelia burgdorferi Keeps Moving and Carries on: A Review of Borrelial Dissemination and Invasion","volume":"8","author":"JA Hyde","year":"2017","journal-title":"Front 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burgdorferi","volume":"35","author":"S Casjens","year":"2000","journal-title":"Molecular microbiology"},{"issue":"6660","key":"ppat.1009869.ref009","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/37551","article-title":"Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi","volume":"390","author":"CM Fraser","year":"1997","journal-title":"Nature"},{"issue":"3","key":"ppat.1009869.ref010","doi-asserted-by":"crossref","first-page":"e33280","DOI":"10.1371\/journal.pone.0033280","article-title":"Genome stability of Lyme disease spirochetes: comparative genomics of Borrelia burgdorferi plasmids","volume":"7","author":"SR Casjens","year":"2012","journal-title":"PloS one"},{"issue":"6","key":"ppat.1009869.ref011","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1111\/cmi.12138","article-title":"Microbial quest for food in vivo: \u2019nutritional virulence\u2019 as an emerging paradigm.","volume":"15","author":"Y Abu Kwaik","year":"2013","journal-title":"Cell Microbiol"},{"key":"ppat.1009869.ref012","first-page":"473","volume":"42","author":"J Coburn","year":"2021","journal-title":"Lyme Disease Pathogenesis. 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Jain","year":"2012","journal-title":"Infection and immunity"},{"issue":"9","key":"ppat.1009869.ref016","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1073\/pnas.0812999106","article-title":"A manganese transporter, BB0219 (BmtA), is required for virulence by the Lyme disease spirochete, Borrelia burgdorferi","volume":"106","author":"Z Ouyang","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"11","key":"ppat.1009869.ref017","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1128\/IAI.00430-16","article-title":"Gene bb0318 is critical for the oxidative stress response and infectivity of Borrelia burgdorferi","volume":"84","author":"AC Showman","year":"2016","journal-title":"Infection and immunity"},{"issue":"7","key":"ppat.1009869.ref018","doi-asserted-by":"crossref","first-page":"e1002102","DOI":"10.1371\/journal.ppat.1002102","article-title":"Borrelia burgdorferi requires glycerol for maximum 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properties as eukaryotic lipid rafts","volume":"9","author":"TJ LaRocca","year":"2013","journal-title":"Plos Pathog"},{"issue":"2","key":"ppat.1009869.ref025","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1365-2958.2011.07932.x","article-title":"The BB0646 protein demonstrates lipase and haemolytic activity associated with Borrelia burgdorferi, the aetiological agent of Lyme disease","volume":"83","author":"DK Shaw","year":"2012","journal-title":"Molecular microbiology"},{"key":"ppat.1009869.ref026","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/978-1-4939-7383-5_12","article-title":"Selection of Borrelia burgdorferi Promoter Sequences Active During Mammalian Infection Using In Vivo Expression Technology","volume":"1690","author":"PP Adams","year":"2018","journal-title":"Methods Mol Biol"},{"issue":"6","key":"ppat.1009869.ref027","article-title":"In Vivo Expression Technology Identifies a Novel Virulence Factor Critical for Borrelia burgdorferi Persistence in Mice","volume":"10","author":"TC Ellis","year":"2014","journal-title":"Plos Pathog"},{"issue":"2","key":"ppat.1009869.ref028","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1093\/nar\/gkw1180","article-title":"In vivo expression technology and 5\u2019 end mapping of the Borrelia burgdorferi transcriptome identify novel RNAs expressed during mammalian infection","volume":"45","author":"PP Adams","year":"2017","journal-title":"Nucleic acids research"},{"key":"ppat.1009869.ref029","doi-asserted-by":"crossref","first-page":"D222","DOI":"10.1093\/nar\/gku1221","article-title":"CDD: NCBI\u2019s conserved domain database","volume":"43","author":"A Marchler-Bauer","year":"2015","journal-title":"Nucleic acids research"},{"key":"ppat.1009869.ref030","first-page":"166","article-title":"TMbase\u2014A database of membrane spanning protein segments","volume":"374","author":"K Hofmann","year":"1993","journal-title":"Biol Chem"},{"issue":"2","key":"ppat.1009869.ref031","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1006\/jmbi.1998.2107","article-title":"Principles governing amino acid composition of integral membrane proteins: application to topology prediction","volume":"283","author":"GE Tusnady","year":"1998","journal-title":"J Mol Biol"},{"issue":"9","key":"ppat.1009869.ref032","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1093\/bioinformatics\/17.9.849","article-title":"The HMMTOP transmembrane topology prediction server","volume":"17","author":"GE Tusnady","year":"2001","journal-title":"Bioinformatics"},{"issue":"10","key":"ppat.1009869.ref033","doi-asserted-by":"crossref","first-page":"4556","DOI":"10.1021\/pr200395b","article-title":"Characterization of multiprotein complexes of the Borrelia burgdorferi outer membrane vesicles","volume":"10","author":"X Yang","year":"2011","journal-title":"J Proteome Res"},{"issue":"6","key":"ppat.1009869.ref034","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/pmic.201100211","article-title":"Comparative membrane proteome analysis of three Borrelia species","volume":"12","author":"B Gesslbauer","year":"2012","journal-title":"Proteomics"},{"key":"ppat.1009869.ref035","first-page":"87","article-title":"Borrelia burgdorferi bbk13 Is critical for spirochete population expansion in the skin during early Infection","author":"GF Aranjuez","year":"2019","journal-title":"Infection and immunity"},{"issue":"10","key":"ppat.1009869.ref036","doi-asserted-by":"crossref","first-page":"6477","DOI":"10.4049\/jimmunol.174.10.6477","article-title":"Human lymphoid and myeloid cell development in NOD\/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells","volume":"174","author":"LD Shultz","year":"2005","journal-title":"J Immunol"},{"issue":"9","key":"ppat.1009869.ref037","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1099\/mic.0.000673","article-title":"Isolation of colonization-defective Escherichia coli mutants reveals critical requirement for fatty acids in bacterial colony formation","volume":"164","author":"K Nosho","year":"2018","journal-title":"Microbiology (Reading)"},{"key":"ppat.1009869.ref038","first-page":"213","article-title":"Determining the cellular targets of reactive oxygen species in Borrelia burgdorferi","volume":"431","author":"JA Boylan","year":"2008","journal-title":"Methods Mol Biol"},{"key":"ppat.1009869.ref039","unstructured":"Edwards M, Mohiuddin SS. Biochemistry, Lipolysis. StatPearls. Treasure Island (FL)2021."},{"issue":"1","key":"ppat.1009869.ref040","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1574-6976.1994.tb00121.x","article-title":"Bacterial lipases","volume":"15","author":"KE Jaeger","year":"1994","journal-title":"FEMS Microbiol Rev"},{"issue":"6","key":"ppat.1009869.ref041","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.plipres.2004.09.002","article-title":"GDSL family of serine esterases\/lipases","volume":"43","author":"CC Akoh","year":"2004","journal-title":"Prog Lipid Res"},{"key":"ppat.1009869.ref042","volume-title":"Aerobic Utilization of Hydrocarbons, Oils and Lipids Handbook of Hydrocarbon and Lipid Microbiology","author":"F Kovacic","year":"2019"},{"key":"ppat.1009869.ref043","doi-asserted-by":"crossref","first-page":"63","DOI":"10.4103\/jrms.JRMS_904_17","article-title":"Mycobacterium tuberculosis and lipids: Insights into molecular mechanisms from persistence to virulence","volume":"23","author":"C. Ghazaei","year":"2018","journal-title":"J Res Med Sci"},{"issue":"Pt 10","key":"ppat.1009869.ref044","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1099\/00221287-148-10-2967","article-title":"Re-annotation of the genome sequence of Mycobacterium tuberculosis H37Rv.","volume":"148","author":"JC Camus","year":"2002","journal-title":"Microbiology (Reading)"},{"issue":"6685","key":"ppat.1009869.ref045","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/31159","article-title":"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence","volume":"393","author":"ST Cole","year":"1998","journal-title":"Nature"},{"issue":"2","key":"ppat.1009869.ref046","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1046\/j.1365-2958.1999.01593.x","article-title":"Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis","volume":"34","author":"LR Camacho","year":"1999","journal-title":"Molecular microbiology"},{"issue":"25","key":"ppat.1009869.ref047","doi-asserted-by":"crossref","first-page":"18348","DOI":"10.1074\/jbc.M700035200","article-title":"Characterization of a novel cell wall-anchored protein with carboxylesterase activity required for virulence in Mycobacterium tuberculosis","volume":"282","author":"S Lun","year":"2007","journal-title":"The Journal of biological chemistry"},{"issue":"3","key":"ppat.1009869.ref048","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1128\/IAI.71.3.1379-1388.2003","article-title":"Isolation of acid-inducible genes of Mycobacterium tuberculosis with the use of recombinase-based in vivo expression technology","volume":"71","author":"B Saviola","year":"2003","journal-title":"Infection and immunity"},{"key":"ppat.1009869.ref049","first-page":"88","article-title":"Mycobacterium tuberculosis LipE Has a Lipase\/Esterase Activity and Is Important for Intracellular Growth and In Vivo Infection","author":"D Yang","year":"2019","journal-title":"Infection and immunity"},{"issue":"1","key":"ppat.1009869.ref050","doi-asserted-by":"crossref","first-page":"e53657","DOI":"10.1371\/journal.pone.0053657","article-title":"Human granuloma in vitro model, for TB dormancy and resuscitation","volume":"8","author":"N Kapoor","year":"2013","journal-title":"PloS one"},{"issue":"20","key":"ppat.1009869.ref051","doi-asserted-by":"crossref","first-page":"5858","DOI":"10.1128\/JB.05765-11","article-title":"The lipase LipA (PA2862) but not LipC (PA4813) from Pseudomonas aeruginosa influences regulation of pyoverdine production and expression of the sigma factor PvdS","volume":"193","author":"H Funken","year":"2011","journal-title":"Journal of bacteriology"},{"issue":"1","key":"ppat.1009869.ref052","first-page":"25","article-title":"Lipase LipC affects motility, biofilm formation and rhamnolipid production in Pseudomonas aeruginosa","volume":"309","author":"F Rosenau","year":"2010","journal-title":"FEMS microbiology letters"},{"issue":"6","key":"ppat.1009869.ref053","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.ijmm.2017.11.013","article-title":"Staphylococcal (phospho)lipases promote biofilm formation and host cell invasion","volume":"308","author":"MT Nguyen","year":"2018","journal-title":"Int J Med Microbiol"},{"issue":"5","key":"ppat.1009869.ref054","first-page":"106","article-title":"Phospholipases in bacterial virulence and pathogenesis","volume":"10","author":"K Bandana","year":"2018","journal-title":"Adv Biotech & Micro"},{"issue":"1","key":"ppat.1009869.ref055","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12866-016-0762-z","article-title":"Consensus computational network analysis for identifying candidate outer membrane proteins from Borrelia spirochetes","volume":"16","author":"MR Kenedy","year":"2016","journal-title":"BMC microbiology"},{"issue":"11","key":"ppat.1009869.ref056","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1093\/infdis\/jiw013","article-title":"A Borrelia burgdorferi Surface-Exposed Transmembrane Protein Lacking Detectable Immune Responses Supports Pathogen Persistence and Constitutes a Vaccine Target","volume":"213","author":"F Kung","year":"2016","journal-title":"J Infect Dis"},{"issue":"2","key":"ppat.1009869.ref057","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00803-16","article-title":"Outer Membrane Proteins BB0405 and BB0406 Are Immunogenic, but Only BB0405 Is Required for Borrelia burgdorferi Infection","volume":"85","author":"B Shrestha","year":"2017","journal-title":"Infection and immunity"},{"key":"ppat.1009869.ref058","article-title":"The Borrelia afzelii outer membrane protein BAPKO_0422 binds human Factor-H and is predicted to form a membrane-spanning \u03b2-barrel","author":"A Dyer","year":"2015","journal-title":"Bioscience 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Revel","year":"2002","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"3","key":"ppat.1009869.ref062","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/mmi.12882","article-title":"Stage-specific global alterations in the transcriptomes of Lyme disease spirochetes during tick feeding and following mammalian host adaptation","volume":"95","author":"R Iyer","year":"2015","journal-title":"Molecular microbiology"},{"key":"ppat.1009869.ref063","first-page":"88","article-title":"Mycoplasma bovis Membrane Protein MilA Is a Multifunctional Lipase with Novel Lipid and Glycosaminoglycan Binding Activity","author":"JY Adamu","year":"2020","journal-title":"Infection and immunity"},{"issue":"8","key":"ppat.1009869.ref064","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1128\/JB.01281-13","article-title":"Characterization of the Vibrio cholerae VolA surface-exposed lipoprotein 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Escherichia coli 5\u2019 UTR and ORF-internal RNAs detected by 3\u2019 end mapping","volume":"10","author":"PP Adams","year":"2021","journal-title":"Elife"},{"issue":"3","key":"ppat.1009869.ref073","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1046\/j.1365-2958.2001.02256.x","article-title":"Isolation of a circular plasmid region sufficient for autonomous replication and transformation of infectious Borrelia burgdorferi","volume":"39","author":"PE Stewart","year":"2001","journal-title":"Molecular microbiology"},{"issue":"1","key":"ppat.1009869.ref074","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1159\/000073406","article-title":"New antibiotic resistance cassettes suitable for genetic studies in Borrelia burgdorferi","volume":"6","author":"AF Elias","year":"2003","journal-title":"Journal of molecular microbiology and 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Skare","year":"1995","journal-title":"The Journal of clinical investigation"},{"issue":"4","key":"ppat.1009869.ref084","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1128\/JB.01236-13","article-title":"Structural modeling and physicochemical characterization provide evidence that P66 forms a beta-barrel in the Borrelia burgdorferi outer membrane","volume":"196","author":"MR Kenedy","year":"2014","journal-title":"Journal of bacteriology"},{"issue":"3","key":"ppat.1009869.ref085","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/j.1365-2958.2009.07015.x","article-title":"Borrelia burgdorferi locus BB0795 encodes a BamA orthologue required for growth and efficient localization of outer membrane proteins","volume":"75","author":"TR Lenhart","year":"2010","journal-title":"Molecular microbiology"},{"issue":"Pt 4","key":"ppat.1009869.ref086","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1099\/00221287-144-4-1033","article-title":"Oligopeptide permease in Borrelia burgdorferi: putative peptide-binding components encoded by both chromosomal and plasmid loci","volume":"144","author":"JL Bono","year":"1998","journal-title":"Microbiology"},{"issue":"6","key":"ppat.1009869.ref087","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1128\/IAI.67.6.2874-2883.1999","article-title":"Access of antibody or trypsin to an integral outer membrane protein (P66) of Borrelia burgdorferi is hindered by Osp lipoproteins","volume":"67","author":"J Bunikis","year":"1999","journal-title":"Infection and immunity"},{"issue":"11","key":"ppat.1009869.ref088","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1128\/iai.57.11.3445-3451.1989","article-title":"Antibody response in white-footed mice (Peromyscus leucopus) experimentally infected with the Lyme disease spirochete (Borrelia burgdorferi)","volume":"57","author":"TG Schwan","year":"1989","journal-title":"Infection and 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