{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:46:05Z","timestamp":1789883165507,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013361","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000}}],"reference-count":96,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI133367"],"award-info":[{"award-number":["AI133367"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI146930"],"award-info":[{"award-number":["AI146930"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic><jats:italic>Borreliella burgdorferi<\/jats:italic><\/jats:italic>, the causative agent of Lyme disease, has evolved unique complement evasion proteins that promote its ability to establish and maintain infection in mammalian hosts. Among these is <jats:italic><jats:italic>B. burgdorferi<\/jats:italic><\/jats:italic> BBK32, a multifunctional surface lipoprotein that binds extracellular matrix (ECM) components, including fibronectin (Fn). In addition to its ECM-binding functions, BBK32 binds to C1r, the initiator protease of the classical pathway of complement, and protects <jats:italic><jats:italic>B. burgdorferi<\/jats:italic><\/jats:italic> from complement-mediated killing following exposure to normal human serum. The disparate functions of BBK32 in adhesion and complement evasion have previously been studied in isolation. Herein we demonstrate that full-length BBK32 binds both Fn and C1 concurrently, indicating that binding of these macromolecules do not sterically hinder their simultaneous interaction. Given the link of antibody dependence to the classical pathway, we tested how the presence of BBK32 would protect infectious <jats:italic><jats:italic>B. burgdorferi<\/jats:italic><\/jats:italic> from borrelial-specific antibodies in a complement-dependent manner. BBK32 provided protection against complement activation in the presence of borrelial-specific antibodies <jats:italic><jats:italic>in vitro<\/jats:italic><\/jats:italic>. We also demonstrated, using both flow cytometry and fluorescence microscopy, that BBK32 results in the reduction of C4 deposition on the surface of borrelial cells. This work demonstrates that BBK32 can simultaneously bind to both C1r and Fn and contributes to the broader understanding of the ability of <jats:italic><jats:italic>B. burgdorferi<\/jats:italic><\/jats:italic> to evade antibody-dependent complement-mediated killing. These observations are significant as they suggest that BBK32 plays a dual role in adhesion and dissemination in infectious <jats:italic><jats:italic>B. burgdorferi<\/jats:italic><\/jats:italic>, as well as immune evasion activities, which ostensibly promotes its pathogenic potential.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013361","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T17:44:07Z","timestamp":1753379047000},"page":"e1013361","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["BBK32 attenuates antibody-dependent complement-mediated killing of infectious Borreliella burgdorferi isolates"],"prefix":"10.1371","volume":"21","author":[{"given":"Alexandra D.","family":"Powell-Pierce","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Booth, Jr.","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payton G.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany L.","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon S.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon L.","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8378-7862","authenticated-orcid":true,"given":"Jon T.","family":"Skare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"issue":"2","key":"ppat.1013361.ref001","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.idc.2015.02.010","article-title":"Epidemiology of Lyme disease","volume":"29","author":"PS Mead","year":"2015","journal-title":"Infect Dis Clin North Am"},{"key":"ppat.1013361.ref002","first-page":"333","article-title":"Lyme Disease in Humans","volume":"42","author":"JD Radolf","year":"2021","journal-title":"Curr Issues Mol Biol"},{"issue":"2","key":"ppat.1013361.ref003","doi-asserted-by":"crossref","first-page":"616","DOI":"10.3201\/eid2702.202731","article-title":"Estimating the Frequency of Lyme Disease Diagnoses, United States, 2010-2018","volume":"27","author":"KJ Kugeler","year":"2021","journal-title":"Emerg Infect 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Coburn","year":"2021"},{"issue":"2","key":"ppat.1013361.ref007","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1172\/JCI200419894","article-title":"OspC facilitates Borrelia burgdorferi invasion of Ixodes scapularis salivary glands","volume":"113","author":"U Pal","year":"2004","journal-title":"J Clin Invest"},{"issue":"5","key":"ppat.1013361.ref008","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1084\/jem.20031960","article-title":"Essential role for OspA\/B in the life cycle of the Lyme disease spirochete","volume":"199","author":"XF Yang","year":"2004","journal-title":"J Exp Med"},{"issue":"9","key":"ppat.1013361.ref009","doi-asserted-by":"crossref","first-page":"3844","DOI":"10.1128\/IAI.00467-08","article-title":"Essential role of the response regulator Rrp2 in the infectious cycle of Borrelia burgdorferi","volume":"76","author":"BK Boardman","year":"2008","journal-title":"Infect Immun"},{"key":"ppat.1013361.ref010","first-page":"385","article-title":"Live 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Skare","year":"2020","journal-title":"Trends Microbiol"},{"issue":"3","key":"ppat.1013361.ref027","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.pt.2012.12.001","article-title":"Complement evasion by Borrelia burgdorferi: it takes three to tango","volume":"29","author":"SW de Taeye","year":"2013","journal-title":"Trends Parasitol"},{"key":"ppat.1013361.ref028","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3389\/fimmu.2016.00385","article-title":"Hide and Seek: How Lyme Disease Spirochetes Overcome Complement Attack","volume":"7","author":"P Kraiczy","year":"2016","journal-title":"Front Immunol"},{"key":"ppat.1013361.ref029","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ijmm.2007.10.002","article-title":"Borrelia burgdorferi complement regulator-acquiring surface proteins (BbCRASPs): Expression patterns during the mammal-tick infection cycle","author":"T Bykowski","year":"2008","journal-title":"Int J Med 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Microbiol"},{"issue":"6","key":"ppat.1013361.ref035","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.1128\/IAI.71.6.3587-3596.2003","article-title":"Analysis of the OspE determinants involved in binding of factor H and OspE-targeting antibodies elicited during Borrelia burgdorferi infection in mice","volume":"71","author":"MS Metts","year":"2003","journal-title":"Infect Immun"},{"issue":"3","key":"ppat.1013361.ref036","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":"Mol Microbiol"},{"issue":"5","key":"ppat.1013361.ref037","doi-asserted-by":"crossref","DOI":"10.1172\/JCI166710","article-title":"BosR and PlzA reciprocally regulate RpoS function to sustain Borrelia burgdorferi in ticks and mammals","volume":"133","author":"AA Grassmann","year":"2023","journal-title":"J Clin Invest"},{"issue":"6","key":"ppat.1013361.ref038","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.molimm.2009.11.028","article-title":"Binding of the complement inhibitor C4b-binding protein to Lyme disease Borreliae","volume":"47","author":"J Pietik\u00e4inen","year":"2010","journal-title":"Mol Immunol"},{"issue":"12","key":"ppat.1013361.ref039","doi-asserted-by":"crossref","DOI":"10.1111\/cmi.12786","article-title":"Borrelia burgdorferi outer surface protein C (OspC) binds complement component C4b and confers bloodstream survival","volume":"19","author":"JA Caine","year":"2017","journal-title":"Cell Microbiol"},{"issue":"5","key":"ppat.1013361.ref040","doi-asserted-by":"crossref","first-page":"107236","DOI":"10.1016\/j.jbc.2024.107236","article-title":"The molecular determinants of classical pathway complement inhibition by OspEF-related proteins of Borrelia burgdorferi","volume":"300","author":"S Thomas","year":"2024","journal-title":"J Biol Chem"},{"issue":"11","key":"ppat.1013361.ref041","doi-asserted-by":"crossref","first-page":"102557","DOI":"10.1016\/j.jbc.2022.102557","article-title":"Outer surface lipoproteins from the Lyme disease spirochete exploit the molecular switch mechanism of the complement protease C1s","volume":"298","author":"RJ Garrigues","year":"2022","journal-title":"J Biol Chem"},{"issue":"13","key":"ppat.1013361.ref042","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2117770119","article-title":"Lipoproteome screening of the Lyme disease agent identifies inhibitors of antibody-mediated complement killing","volume":"119","author":"MJ Pereira","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"ppat.1013361.ref043","doi-asserted-by":"crossref","first-page":"104972","DOI":"10.1016\/j.jbc.2023.104972","article-title":"Conformational dynamics of complement protease C1r inhibitor proteins from Lyme disease- and relapsing fever-causing spirochetes","volume":"299","author":"S Roy","year":"2023","journal-title":"J Biol Chem"},{"issue":"11","key":"ppat.1013361.ref044","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.4049\/jimmunol.2100815","article-title":"A Structural Basis for Inhibition of the Complement Initiator Protease C1r by Lyme Disease Spirochetes","volume":"207","author":"RJ Garrigues","year":"2021","journal-title":"J Immunol"},{"issue":"3","key":"ppat.1013361.ref045","article-title":"Structural determination of the complement inhibitory domain of Borrelia burgdorferi BBK32 provides insight into classical pathway complement evasion by Lyme disease spirochetes","volume":"15","author":"J Xie","year":"2019","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1013361.ref046","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005404","article-title":"Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex","volume":"12","author":"BL Garcia","year":"2016","journal-title":"PLoS Pathog"},{"issue":"5","key":"ppat.1013361.ref047","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1111\/j.1365-2958.2005.05042.x","article-title":"Inactivation of the fibronectin-binding adhesin gene bbk32 significantly attenuates the infectivity potential of Borrelia burgdorferi","volume":"59","author":"J Seshu","year":"2006","journal-title":"Mol Microbiol"},{"issue":"5","key":"ppat.1013361.ref048","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1046\/j.1365-2958.1998.01127.x","article-title":"Identification of a 47\u2009kDa fibronectin-binding protein expressed by Borrelia burgdorferi isolate B31","volume":"30","author":"WS Probert","year":"1998","journal-title":"Mol Microbiol"},{"issue":"6","key":"ppat.1013361.ref049","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.1128\/IAI.69.6.4129-4133.2001","article-title":"Mapping the ligand-binding region of Borrelia burgdorferi 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Borrelia burgdorferi in vivo demonstrates that the fibronectin-binding protein BBK32 is required for optimal infectivity","volume":"82","author":"JA Hyde","year":"2011","journal-title":"Mol Microbiol"},{"issue":"10","key":"ppat.1013361.ref053","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1016\/j.celrep.2016.08.013","article-title":"Biomechanics of Borrelia burgdorferi Vascular Interactions","volume":"16","author":"R Ebady","year":"2016","journal-title":"Cell Rep"},{"issue":"5","key":"ppat.1013361.ref054","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1111\/mmi.12045","article-title":"Vascular binding of a pathogen under shear force through mechanistically distinct sequential interactions with host macromolecules","volume":"86","author":"TJ Moriarty","year":"2012","journal-title":"Mol Microbiol"},{"issue":"1","key":"ppat.1013361.ref055","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1128\/IAI.74.1.435-441.2006","article-title":"Fibronectin binding 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spirochete Borrelia burgdorferi","volume":"47","author":"DS Samuels","year":"1995","journal-title":"Methods Mol Biol"},{"key":"ppat.1013361.ref065","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/978-1-4939-7383-5_15","article-title":"Genetic Transformation and Complementation","volume":"1690","author":"DS Samuels","year":"2018","journal-title":"Methods Mol Biol"},{"key":"ppat.1013361.ref066","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","article-title":"A guided tour into subcellular colocalization analysis in light microscopy","volume":"224","author":"S Bolte","year":"2006","journal-title":"J Microsc"},{"issue":"19","key":"ppat.1013361.ref067","doi-asserted-by":"crossref","first-page":"18803","DOI":"10.1074\/jbc.M501731200","article-title":"Borrelia burgdorferi binds fibronectin through a tandem beta-zipper, a common mechanism of fibronectin binding in staphylococci, streptococci, and spirochetes","volume":"280","author":"S Raibaud","year":"2005","journal-title":"J Biol Chem"},{"issue":"4","key":"ppat.1013361.ref068","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0005412","article-title":"A novel fibronectin binding motif in MSCRAMMs targets F3 modules","volume":"4","author":"S Prabhakaran","year":"2009","journal-title":"PLoS One"},{"issue":"7","key":"ppat.1013361.ref069","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0159118","article-title":"Allosteric Regulation of Fibronectin\/\u03b15\u03b21 Interaction by Fibronectin-Binding MSCRAMMs","volume":"11","author":"X Liang","year":"2016","journal-title":"PLoS One"},{"issue":"4","key":"ppat.1013361.ref070","article-title":"On-Off Kinetics of Engagement of FNI Modules of Soluble Fibronectin by \u03b2-Strand Addition","volume":"10","author":"W Ma","year":"2015","journal-title":"PLoS One"},{"issue":"8","key":"ppat.1013361.ref071","doi-asserted-by":"crossref","first-page":"4608","DOI":"10.1128\/IAI.71.8.4608-4613.2003","article-title":"The 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Bing","year":"1982","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"ppat.1013361.ref080","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.4049\/jimmunol.134.3.1844","article-title":"Characterization of the opsonic and monocyte adherence functions of the specific fibronectin fragment that enhances phagocytosis of particulate activators","volume":"134","author":"JK Czop","year":"1985","journal-title":"J Immunol"},{"issue":"1","key":"ppat.1013361.ref081","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12865-020-00393-6","article-title":"Extracellular signal-regulated kinase 1\/2 is required for complement component C1q and fibronectin dependent enhancement of Fc\u03b3- receptor mediated phagocytosis in mouse and human cells","volume":"21","author":"EA Willmann","year":"2020","journal-title":"BMC Immunol"},{"key":"ppat.1013361.ref082","doi-asserted-by":"crossref","first-page":"442","DOI":"10.3389\/fimmu.2016.00442","article-title":"Multifunctional and Redundant Roles of Borrelia burgdorferi Outer Surface Proteins in Tissue Adhesion, Colonization, and Complement Evasion","volume":"7","author":"JA Caine","year":"2016","journal-title":"Front Immunol"},{"issue":"12","key":"ppat.1013361.ref083","doi-asserted-by":"crossref","first-page":"7800","DOI":"10.1128\/IAI.69.12.7800-7809.2001","article-title":"Further characterization of complement regulator-acquiring surface proteins of Borrelia burgdorferi","volume":"69","author":"P Kraiczy","year":"2001","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1013361.ref084","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1074\/jbc.M308343200","article-title":"Complement resistance of Borrelia burgdorferi correlates with the expression of BbCRASP-1, a novel linear plasmid-encoded surface protein that interacts with human factor H and FHL-1 and is unrelated to Erp proteins","volume":"279","author":"P Kraiczy","year":"2004","journal-title":"J Biol 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Disease","volume":"10","author":"L Walter","year":"2019","journal-title":"Front Immunol"},{"key":"ppat.1013361.ref088","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fimmu.2017.00012","article-title":"Host Immune Evasion by Lyme and Relapsing Fever Borreliae: Findings to Lead Future Studies for Borrelia miyamotoi","volume":"8","author":"BL Stone","year":"2017","journal-title":"Front Immunol"},{"issue":"1","key":"ppat.1013361.ref089","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41598-017-00412-4","article-title":"Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties","volume":"7","author":"F R\u00f6ttgerding","year":"2017","journal-title":"Sci Rep"},{"issue":"6","key":"ppat.1013361.ref090","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0000698","article-title":"Human complement regulators C4b-binding protein and C1 esterase inhibitor interact with a novel outer surface protein of Borrelia recurrentis","volume":"4","author":"S Grosskinsky","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"issue":"5","key":"ppat.1013361.ref091","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1128\/IAI.00089-10","article-title":"Molecular characterization of the interaction of Borrelia parkeri and Borrelia turicatae with human complement regulators","volume":"78","author":"M Schott","year":"2010","journal-title":"Infect Immun"},{"issue":"8","key":"ppat.1013361.ref092","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1128\/IAI.01892-14","article-title":"The Borrelia hermsii factor H binding protein FhbA is not required for infectivity in mice or for resistance to human complement in vitro","volume":"82","author":"LM Fine","year":"2014","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1013361.ref093","doi-asserted-by":"crossref","DOI":"10.1128\/AEM.02519-20","article-title":"A CRISPR interference platform for selective 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