{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:38:33Z","timestamp":1777588713298,"version":"3.51.4"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>We recently demonstrated that TP_0326 is a bona fide rare outer membrane protein (OMP) in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Treponema pallidum<\/jats:named-content>and that it possesses characteristic BamA bipartite topology. Herein, we used immunofluorescence analysis (IFA) to show that only the \u03b2-barrel domain of TP_0326 contains surface-exposed epitopes in intact<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. pallidum<\/jats:named-content>. Using the solved structure of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Neisseria gonorrhoeae<\/jats:named-content>BamA, we generated a homology model of full-length TP_0326. Although the model predicts a typical BamA fold, the \u03b2-barrel harbors features not described in other BamAs. Structural modeling predicted that a dome comprised of three large extracellular loops, loop 4 (L4), L6, and L7, covers the barrel's extracellular opening. L4, the dome's major surface-accessible loop, contains mainly charged residues, while L7 is largely neutral and contains a polyserine tract in a two-tiered conformation. L6 projects into the \u03b2-barrel but lacks the VRGF\/Y motif that anchors L6 within other BamAs. IFA and opsonophagocytosis assay revealed that L4 is surface exposed and an opsonic target. Consistent with B cell epitope predictions, immunoblotting and enzyme-linked immunosorbent assay (ELISA) confirmed that L4 is an immunodominant loop in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. pallidum<\/jats:named-content>-infected rabbits and humans with secondary syphilis. Antibody capture experiments using<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>expressing OM-localized TP_0326 as a<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. pallidum<\/jats:named-content>surrogate further established the surface accessibility of L4. Lastly, we found that a naturally occurring substitution (Leu<jats:sup>593<\/jats:sup>\u2192 Gln<jats:sup>593<\/jats:sup>) in the L4 sequences of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. pallidum<\/jats:named-content>strains affects antibody binding in sera from syphilitic patients. Ours is the first study to employ a \u201cstructure-to-pathogenesis\u201d approach to map the surface topology of a<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. pallidum<\/jats:named-content>OMP within the context of syphilitic infection.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Previously, we reported that TP_0326 is a bona fide rare outer membrane protein (OMP) in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Treponema pallidum<\/jats:named-content>and that it possesses the bipartite topology characteristic of a BamA ortholog. Using a homology model as a guide, we found that TP_0326 displays unique features which presumably relate to its function(s) in the biogenesis of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. pallidum<\/jats:named-content>'s unorthodox OM. The model also enabled us to identify an immunodominant epitope in a large extracellular loop that is both an opsonic target and subject to immune pressure in a human population. Ours is the first study to follow a structure-to-pathogenesis approach to map the surface topology of a<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. pallidum<\/jats:named-content>rare OMP within the context of syphilitic infection.<\/jats:p>","DOI":"10.1128\/jb.00086-15","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T09:37:06Z","timestamp":1427881026000},"page":"1906-1920","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["A Homology Model Reveals Novel Structural Features and an Immunodominant Surface Loop\/Opsonic Target in the Treponema pallidum BamA Ortholog TP_0326"],"prefix":"10.1128","volume":"197","author":[{"given":"Amit","family":"Luthra","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Connecticut Health, Farmington, Connecticut, 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