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To identify potentially protective antibodies against <jats:italic>Treponema pallidum<\/jats:italic> (<jats:italic>TPA<\/jats:italic>), we used <jats:italic>Pyrococcus furiosus<\/jats:italic> thioredoxin (<jats:italic>Pf<\/jats:italic>Trx) to display extracellular loops (ECLs) from three <jats:italic>TPA<\/jats:italic> outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded \u03b2-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). We identified five immunodominant loops from the FadL orthologs TP0856, TP0858 and TP0865 by immunoblotting and ELISA. Rabbits and mice immunized with these five <jats:italic>Pf<\/jats:italic>Trx constructs produced loop-specific antibodies that promoted opsonophagocytosis of <jats:italic>TPA<\/jats:italic> by rabbit peritoneal and murine bone marrow-derived macrophages at levels comparable to IRS and mouse syphilitic serum. Heat-inactivated IRS and loop-specific rabbit and mouse antisera also impaired viability, motility, and cellular attachment of spirochetes during <jats:italic>in vitro<\/jats:italic> cultivation. The results support the use of ECL-based vaccines and suggest that loop-specific antibodies promote spirochete clearance via Fc receptor-independent as well as Fc receptor-dependent mechanisms.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012443","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T18:50:13Z","timestamp":1734979813000},"page":"e1012443","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities"],"prefix":"10.1371","volume":"20","author":[{"given":"Kristina N.","family":"Delgado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Caimano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel C.","family":"Orbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal F.","family":"Vicente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carson J.","family":"La Vake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 A.","family":"Grassmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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Lei","year":"2014","journal-title":"PLoS One"},{"issue":"4","key":"ppat.1012443.ref037","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.4049\/jimmunol.131.4.1973","article-title":"Humoral immune response in experimental syphilis to polypeptides of Treponema pallidum","volume":"131","author":"PA Hanff","year":"1983","journal-title":"J Immunol"},{"issue":"9","key":"ppat.1012443.ref038","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1128\/iai.57.9.2872-2877.1989","article-title":"Major integral membrane protein immunogens of Treponema pallidum are proteolipids","volume":"57","author":"NR Chamberlain","year":"1989","journal-title":"Infection and Immunity"},{"issue":"12","key":"ppat.1012443.ref039","doi-asserted-by":"crossref","first-page":"e0010063","DOI":"10.1371\/journal.pntd.0010063","article-title":"Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in 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Zepp","year":"2010","journal-title":"Vaccine"},{"issue":"6","key":"ppat.1012443.ref052","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1111\/mmi.13747","article-title":"Heterogeneity in non-epitope loop sequence and outer membrane protein complexes alters antibody binding to the major porin protein PorB in serogroup B Neisseria meningitidis","volume":"105","author":"KA Matthias","year":"2017","journal-title":"Mol Microbiol"},{"issue":"7","key":"ppat.1012443.ref053","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.str.2014.05.008","article-title":"Lateral opening and exit pore formation are required for BamA function","volume":"22","author":"N Noinaj","year":"2014","journal-title":"Structure"},{"issue":"2","key":"ppat.1012443.ref054","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1006\/jmbi.2000.3671","article-title":"High-resolution structure of the OmpA membrane domain","volume":"298","author":"A Pautsch","year":"2000","journal-title":"J Mol 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Nelson","year":"1949","journal-title":"J Exp Med"},{"issue":"1","key":"ppat.1012443.ref067","first-page":"191","article-title":"Humoral immunity in experimental syphilis. I. The demonstration of resistance conferred by passive immunization","volume":"117","author":"NH Bishop","year":"1976","journal-title":"J Immunol"},{"issue":"3","key":"ppat.1012443.ref068","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1128\/iai.44.3.740-742.1984","article-title":"Cobra venom factor abrogates passive humoral resistance to syphilitic infection in hamsters","volume":"44","author":"AA Azadegan","year":"1984","journal-title":"Infect Immun"},{"issue":"5","key":"ppat.1012443.ref069","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1128\/iai.13.5.1402-1407.1976","article-title":"Immunity to syphilis: passive transfer in rabbits using serial doses of immune serum","volume":"13","author":"RS Weiser","year":"1976","journal-title":"Infect Immun"},{"issue":"5","key":"ppat.1012443.ref070","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1128\/iai.8.5.787-790.1973","article-title":"Immunity to syphilis. I. Passive transfer in rabbits with hyperimmune serum","volume":"8","author":"PL Perine","year":"1973","journal-title":"Infect Immun"},{"issue":"8","key":"ppat.1012443.ref071","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00323-19","article-title":"Evaluation of the protective ability of the Treponema pallidum subsp. pallidum Tp0126 OmpW homolog in the rabbit model of syphilis","volume":"87","author":"AM Haynes","year":"2019","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1012443.ref072","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1084\/jem.189.4.647","article-title":"Treponema pallidum major sheath protein homologue TprK is a target of opsonic antibody and the protective immune response","volume":"189","author":"A Centurion-Lara","year":"1999","journal-title":"J Exp Med"},{"issue":"4","key":"ppat.1012443.ref073","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1086\/315399","article-title":"Opsonic potential, protective capacity, and sequence conservation of the Treponema pallidum subspecies pallidum Tp92","volume":"181","author":"CE Cameron","year":"2000","journal-title":"J Infect Dis"},{"issue":"8","key":"ppat.1012443.ref074","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.micinf.2004.04.001","article-title":"Subfamily I Treponema pallidum repeat protein family: sequence variation and immunity","volume":"6","author":"ES Sun","year":"2004","journal-title":"Microbes Infect"},{"issue":"4","key":"ppat.1012443.ref075","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrmicro.2016.191","article-title":"The \u03b2-barrel assembly machinery in motion","volume":"15","author":"N Noinaj","year":"2017","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"ppat.1012443.ref076","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1038\/s42003-024-06645-0","article-title":"Acinetobacter baumannii OmpA-like porins: functional characterization of bacterial physiology, antibiotic-resistance, and virulence","volume":"7","author":"D Scribano","year":"2024","journal-title":"Communications Biology"},{"issue":"6","key":"ppat.1012443.ref077","first-page":"919","article-title":"Outer membrane protein A and OprF: versatile roles in Gram-negative bacterial infections.","volume":"279","author":"S Krishnan","year":"2012","journal-title":"FEBS J.PubMed Central PMCID"},{"key":"ppat.1012443.ref078","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold\u20093","author":"J Abramson","year":"2024","journal-title":"Nature"},{"key":"ppat.1012443.ref079","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/msb.2011.75","article-title":"Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega","volume":"7","author":"F Sievers","year":"2011","journal-title":"Mol Syst Biol"},{"key":"ppat.1012443.ref080","article-title":"Sickle: A sliding-window, adaptive, quality-based trimming tool for FastQ files (Version 1.33) 2011.","author":"FJ Joshi NA"},{"key":"ppat.1012443.ref081","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4137\/EBO.S11250","article-title":"EDGE-pro: Estimated Degree of Gene Expression in Prokaryotic Genomes.","volume":"9","author":"T Magoc","year":"2013","journal-title":"Evol Bioinform Online"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012443","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012443","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T19:25:15Z","timestamp":1737746715000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012443"}},"subtitle":[],"editor":[{"given":"Thomas","family":"Guillard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,23]]},"references-count":81,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012443","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1012443","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,23]]}}}