{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:49:39Z","timestamp":1791838179920,"version":"4.3.4"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI144177"],"award-info":[{"award-number":["U19AI144177"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-036560"],"award-info":[{"award-number":["INV-036560"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["214641\/Z\/18\/Z"],"award-info":[{"award-number":["214641\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["D43TW006589"],"award-info":[{"award-number":["D43TW006589"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Venereal syphilis, caused by the spirochete <jats:italic>Treponema pallidum<\/jats:italic> subsp. <jats:italic>pallidum<\/jats:italic> (<jats:italic>TPA<\/jats:italic>), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of <jats:italic>TPA<\/jats:italic> strains circulating within at-risk populations. The aim of this study was to describe the clinical, demographic, and molecular features of early syphilis cases in Cali, Colombia.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>We conducted a cross-sectional study to identify individuals with early syphilis (ES) in Cali, Colombia through a city-wide network of public health centers, private sector HIV clinics and laboratory databases from public health institutions. Whole blood (WB), skin biopsies (SB), and genital and oral lesion swabs were obtained for measurement of treponemal burdens by <jats:italic>polA<\/jats:italic> quantitative polymerase chain reaction (qPCR) and for whole-genome sequencing (WGS). Among 1,966 individuals screened, 128 participants met enrollment criteria: 112 (87%) with secondary (SS), 15 (12%) with primary (PS) and one with early latent syphilis; 66\/128 (52%) self-reported as heterosexual, while 48 (38%) were men who have sex with men (MSM). Genital ulcer swabs had the highest <jats:italic>polA<\/jats:italic> copy numbers (67 copies\/\u03bcl) by qPCR with a positivity rate (PR) of 73%, while SS lesions had 42 <jats:italic>polA<\/jats:italic> copies\/\u03bcl with PR of 62%. WB <jats:italic>polA<\/jats:italic> positivity was more frequent in SS than PS (42% vs 7%, respectively; p = 0.009). Isolation of <jats:italic>TPA<\/jats:italic> from WB by rabbit infectivity testing (RIT) was achieved in 5 (56%) of 9 ES WB samples tested. WGS from 33 Cali patient samples, along with 10 other genomic sequences from South America (9 from Peru, 1 from Argentina) used as comparators, confirmed that SS14 was the predominant clade, and that half of all samples had mutations associated with macrolide (<jats:italic>i<\/jats:italic>.<jats:italic>e<\/jats:italic>., azithromycin) resistance. Variability in the outer membrane protein (OMP) and vaccine candidate BamA (TP0326) was mapped onto the protein\u2019s predicted structure from AlphaFold. Despite the presence of mutations in several extracellular loops (ECLs), ECL4, an immunodominant loop and proven opsonic target, was highly conserved in this group of Colombian and South American <jats:italic>TPA<\/jats:italic> isolates.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>This study offers new insights into the sociodemographic and clinical features of venereal syphilis in a highly endemic area of Colombia and illustrates how genomic sequencing of regionally prevalent <jats:italic>TPA<\/jats:italic> strains can inform vaccine development.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0307600","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T17:25:48Z","timestamp":1721409948000},"page":"e0307600","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Treponema pallidum genetic diversity and its implications for targeted vaccine development: A cross-sectional study of early syphilis cases in Southwestern Colombia"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3881-546X","authenticated-orcid":true,"given":"Juan C.","family":"Salazar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3407-4011","authenticated-orcid":true,"given":"Fabio","family":"Vargas-Cely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4784-6519","authenticated-orcid":true,"given":"Jonny A.","family":"Garc\u00eda-Luna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lady G.","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everton B.","family":"Bettin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson","family":"Romero-Rosas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda F.","family":"Am\u00f3rtegui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e1n","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Oviedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Vigil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carson J.","family":"La Vake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximena","family":"Galindo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose D.","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5641-2392","authenticated-orcid":true,"given":"Alvaro J.","family":"Mart\u00ednez-Valencia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Caimano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Hennelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhang","family":"Aghakhanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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Sexually Transmitted Infections (STIs) https:\/\/www.who.int\/news-room\/factsheets\/detail\/sexually-transmitted-infections-(stis): World health Organization; 2021 [Available from: https:\/\/www.who.int\/news-room\/factsheets\/detail\/sexually-transmitted-infections-(stis)]."},{"key":"pone.0307600.ref003","unstructured":"Pan American Health Organization. Epidemiological Review of Syphilis in the Americas, December 2021. https:\/\/iris.paho.org\/bitstream\/handle\/10665.2\/56085\/PAHOCDEHT220009_eng.pdf?sequence=1&isAllowed=y2021."},{"issue":"2","key":"pone.0307600.ref004","doi-asserted-by":"crossref","first-page":"e1001396","DOI":"10.1371\/journal.pmed.1001396","article-title":"Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data","volume":"10","author":"L Newman","year":"2013","journal-title":"PLoS Med"},{"key":"pone.0307600.ref005","article-title":"A road map for the global elimination of congenital syphilis","volume":"2010","author":"ML Kamb","year":"2010","journal-title":"Obstet Gynecol Int"},{"issue":"7","key":"pone.0307600.ref006","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1097\/01.olq.0000261456.09797.1b","article-title":"The need and plan for global elimination of congenital syphilis","volume":"34","author":"GP Schmid","year":"2007","journal-title":"Sex Transm Dis"},{"issue":"2","key":"pone.0307600.ref007","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s12519-010-0028-z","article-title":"Congenital syphilis: still a serious, under-diagnosed threat for children in resource-poor countries","volume":"6","author":"C Kruger","year":"2010","journal-title":"World J Pediatr"},{"issue":"3","key":"pone.0307600.ref008","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.siny.2007.01.019","article-title":"Congenital syphilis: a continuing but neglected problem","volume":"12","author":"GJ Walker","year":"2007","journal-title":"Semin Fetal Neonatal Med"},{"issue":"3","key":"pone.0307600.ref009","doi-asserted-by":"crossref","first-page":"e171","DOI":"10.1016\/S2666-5247(22)00041-6","article-title":"Congenital syphilis increases in the USA","volume":"3","author":"R. Nelson","year":"2022","journal-title":"Lancet Microbe"},{"issue":"3","key":"pone.0307600.ref010","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/OLQ.0000000000000792","article-title":"Rapid Increases in Syphilis in Reproductive-Aged Women in Japan: A Warning for Other Countries?","volume":"45","author":"ML Kamb","year":"2018","journal-title":"Sexually Transmitted Diseases"},{"issue":"7","key":"pone.0307600.ref011","doi-asserted-by":"crossref","first-page":"e173","DOI":"10.1016\/S1473-3099(20)30268-1","article-title":"Congenital syphilis, the great imitator\u2014case report and review","volume":"20","author":"MW Keuning","year":"2020","journal-title":"The Lancet Infectious Diseases"},{"issue":"5","key":"pone.0307600.ref012","doi-asserted-by":"crossref","first-page":"e690","DOI":"10.1371\/journal.pntd.0000690","article-title":"Secondary syphilis in cali, Colombia: new concepts in disease pathogenesis","volume":"4","author":"AR Cruz","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"issue":"2","key":"pone.0307600.ref013","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1007\/s10903-007-9081-7","article-title":"Syphilis infection among female sex workers in Colombia","volume":"11","author":"A Mejia","year":"2009","journal-title":"J Immigr Minor Health"},{"issue":"7","key":"pone.0307600.ref014","doi-asserted-by":"crossref","first-page":"e1717","DOI":"10.1371\/journal.pntd.0001717","article-title":"Immune evasion and recognition of the syphilis spirochete in blood and skin of secondary syphilis patients: two immunologically distinct compartments","volume":"6","author":"AR Cruz","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"pone.0307600.ref015","doi-asserted-by":"crossref","DOI":"10.26633\/RPSP.2018.118","article-title":"Prevalence and incidence estimates for syphilis, chlamydia, gonorrhea, and congenital syphilis in Colombia, 1995\u20132016","volume":"42","author":"EL Korenromp","year":"2018","journal-title":"Revista Panamericana de Salud P\u00fablica"},{"issue":"s1","key":"pone.0307600.ref016","first-page":"163","article-title":"Seroreactivity and prevalence of syphilis in donors at a blood bank in Barranquilla, Colombia","volume":"39","author":"JC Martinez-Garces","year":"2019","journal-title":"Biomedica"},{"key":"pone.0307600.ref017","unstructured":"Bonilla-Lucero S. Informe de evento S\u00edfilis Gestacional y Cong\u00e9nita, Colombia, 2021. In: transmisibles. Gde, editor. https:\/\/www.ins.gov.co\/buscador-eventos\/Informesdeevento\/SIFILIS%20INFORME%20FINAL%202021.pdf: Instituto nacional de salud; 2021."},{"key":"pone.0307600.ref018","first-page":"1","article-title":"Laboratory Diagnostic Tools for Syphilis: Current Status and Future Prospects","volume":"10","author":"Y Luo","year":"2021","journal-title":"Frontiers in Cellular and Infection Microbiology"},{"issue":"5","key":"pone.0307600.ref019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jcla.22890","article-title":"PCR detection for syphilis diagnosis: Status and prospects","volume":"33","author":"C Zhou","year":"2019","journal-title":"Journal of Clinical Laboratory Analysis"},{"issue":"2","key":"pone.0307600.ref020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/JCM.01994-20","article-title":"Use of a multiplex PCR assay to assess the presence of treponema pallidum in mucocutaneous ulcerations in patients with suspected syphilis","volume":"59","author":"PA Grange","year":"2021","journal-title":"Journal of Clinical Microbiology"},{"key":"pone.0307600.ref021","doi-asserted-by":"crossref","first-page":"e0000922","DOI":"10.1128\/msphere.00009-22","article-title":"Selective whole-genome amplification as a tool to enrich specimens with low Treponema pallidum genomic DNA copies for whole-genome sequencing","author":"CM Thurlow","year":"2022","journal-title":"mSphere"},{"key":"pone.0307600.ref022","article-title":"Treponema pallidum subspecies pallidum intrapatient homogeneity at various body locations in men with infectious syphilis","author":"HCA Zondag","year":"2022","journal-title":"Microbiol Spectr"},{"issue":"5","key":"pone.0307600.ref023","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1093\/infdis\/jiaa449","article-title":"Analysis of Treponema pallidum strains from China using improved methods for whole-genome sequencing from primary syphilis chancres","volume":"223","author":"W Chen","year":"2021","journal-title":"J Infect Dis"},{"issue":"12","key":"pone.0307600.ref024","first-page":"1","article-title":"Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar","volume":"15","author":"NAP Lieberman","year":"2021","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"pone.0307600.ref025","article-title":"Clinical and genomic diversity of Treponema pallidum subsp","author":"AC Sena","year":"2023","journal-title":"pallidum: A global, multi-center study of early syphilis to inform vaccine research. medRxiv"},{"key":"pone.0307600.ref026","doi-asserted-by":"crossref","first-page":"1007056","DOI":"10.3389\/fmicb.2022.1007056","article-title":"High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny","volume":"13","author":"NAP Lieberman","year":"2022","journal-title":"Front Microbiol"},{"issue":"15","key":"pone.0307600.ref027","doi-asserted-by":"crossref","first-page":"e0008221","DOI":"10.1128\/JB.00082-21","article-title":"Structural modeling of the Treponema pallidum OMPeome: a roadmap for deconvolution of syphilis pathogenesis and development of a syphilis vaccine","volume":"203","author":"KL Hawley","year":"2021","journal-title":"J Bacteriol"},{"key":"pone.0307600.ref028","doi-asserted-by":"crossref","first-page":"e0163922","DOI":"10.1128\/mbio.01639-22","article-title":"Extracellular Loops of the Treponema pallidum FadL Orthologs TP0856 and TP0858 elicit IgG antibodies and IgG(+)-specific B-cells in the rabbit model of experimental syphilis","author":"KN Delgado","year":"2022","journal-title":"mBio"},{"issue":"11","key":"pone.0307600.ref029","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1128\/JB.00086-15","article-title":"A homology model reveals novel structural features and an immunodominant surface loop\/opsonic target in the Treponema pallidum BamA ortholog TP_0326","volume":"197","author":"A Luthra","year":"2015","journal-title":"J Bacteriol"},{"issue":"3","key":"pone.0307600.ref030","article-title":"Sequence Variation of Rare Outer Membrane Protein beta-Barrel Domains in Clinical Strains Provides Insights into the Evolution of Treponema pallidum subsp","volume":"9","author":"S Kumar","year":"2018","journal-title":"pallidum, the Syphilis Spirochete. mBio"},{"key":"pone.0307600.ref031","doi-asserted-by":"crossref","first-page":"1222267","DOI":"10.3389\/fimmu.2023.1222267","article-title":"Use of Epivolve phage display to generate a monoclonal antibody with opsonic activity directed against a subdominant epitope on extracellular loop 4 of Treponema pallidum BamA (TP0326)","volume":"14","author":"MR Ferguson","year":"2023","journal-title":"Front Immunol"},{"issue":"3","key":"pone.0307600.ref032","doi-asserted-by":"crossref","first-page":"e0282492","DOI":"10.1371\/journal.pone.0282492","article-title":"Diagnostic performance of two rapid tests for syphilis screening in people living with HIV in Cali, Colombia","volume":"18","author":"JA Garcia Luna","year":"2023","journal-title":"PLoS One"},{"issue":"1","key":"pone.0307600.ref033","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1093\/infdis\/167.1.148","article-title":"Evaluation of molecular methodologies and rabbit infectivity testing for the diagnosis of congenital syphilis and neonatal central nervous system invasion by Treponema pallidum","volume":"167","author":"PJ Sanchez","year":"1993","journal-title":"J Infect Dis"},{"key":"pone.0307600.ref034","unstructured":"A quality control tool for high throughput sequence data [Internet]. The Babraham Bioinformatics group. 2023. Available from: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"issue":"15","key":"pone.0307600.ref035","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"AM Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"pone.0307600.ref036","unstructured":"Bushnell B, editor BBMap: A Fast, Accurate, Splice-Aware Aligner. Conference: 9th Annual Genomics of Energy & Environment Meeting, Walnut Creek, CA, March 17\u201320, 2014; 2014; United States."},{"key":"pone.0307600.ref037","unstructured":"Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM [Internet]. 2013. Available from: https:\/\/doi.org\/10.48550\/arXiv.1303.3997."},{"issue":"9","key":"pone.0307600.ref038","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"A McKenna","year":"2010","journal-title":"Genome Res"},{"issue":"4","key":"pone.0307600.ref039","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: improvements in performance and usability","volume":"30","author":"K Katoh","year":"2013","journal-title":"Mol Biol Evol"},{"issue":"3","key":"pone.0307600.ref040","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1093\/nar\/gku1196","article-title":"Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins","volume":"43","author":"NJ Croucher","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"pone.0307600.ref041","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1093\/bioinformatics\/btu033","article-title":"RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies","volume":"30","author":"A. Stamatakis","year":"2014","journal-title":"Bioinformatics"},{"issue":"1","key":"pone.0307600.ref042","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1038\/s41467-019-11216-7","article-title":"Genomic epidemiology of syphilis reveals independent emergence of macrolide resistance across multiple circulating lineages","volume":"10","author":"MA Beale","year":"2019","journal-title":"Nat Commun"},{"issue":"12","key":"pone.0307600.ref043","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1038\/s41564-021-01000-z","article-title":"Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis","volume":"6","author":"MA Beale","year":"2021","journal-title":"Nat Microbiol"},{"issue":"D1","key":"pone.0307600.ref044","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"M Varadi","year":"2022","journal-title":"Nucleic Acids Res"},{"issue":"13","key":"pone.0307600.ref045","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014a visualization system for exploratory research and analysis","volume":"25","author":"EF Pettersen","year":"2004","journal-title":"J Comput Chem"},{"issue":"4","key":"pone.0307600.ref046","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr7004a1","article-title":"Sexually transmitted infections, treatment guidelines. 2021","volume":"70","author":"L Workowski KB","year":"2021","journal-title":"MMWR Recomm Rep 2021"},{"issue":"11","key":"pone.0307600.ref047","doi-asserted-by":"crossref","first-page":"855","DOI":"10.7326\/0003-4819-109-11-855","article-title":"Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment","volume":"109","author":"SA Lukehart","year":"1988","journal-title":"Ann Intern Med"},{"key":"pone.0307600.ref048","article-title":"The Treponema pallidum outer membrane","author":"JD Radolf","year":"2017","journal-title":"Curr Top Microbiol Immunol"},{"key":"pone.0307600.ref049","article-title":"Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen","author":"JD Radolf","year":"2016","journal-title":"Nat Rev Microbiol"},{"issue":"6","key":"pone.0307600.ref050","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1111\/j.1365-2958.2011.07662.x","article-title":"TP0326, a Treponema pallidum beta-barrel assembly machinery A (BamA) orthologue and rare outer membrane protein","volume":"80","author":"DC Desrosiers","year":"2011","journal-title":"Mol Microbiol"},{"issue":"6","key":"pone.0307600.ref051","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1086\/511822","article-title":"Treponema pallidum elicits innate and adaptive cellular immune responses in skin and blood during secondary syphilis: a flow-cytometric analysis","volume":"195","author":"JC Salazar","year":"2007","journal-title":"J Infect Dis"},{"issue":"8","key":"pone.0307600.ref052","doi-asserted-by":"crossref","first-page":"O524","DOI":"10.1111\/1469-0691.12504","article-title":"Spirochetemia due to Treponema pallidum using polymerase-chain-reaction assays in patients with early syphilis: prevalence, associated factors and treatment response","volume":"20","author":"BR Wu","year":"2014","journal-title":"Clin Microbiol Infect"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307600","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T17:26:21Z","timestamp":1721409981000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307600"}},"subtitle":[],"editor":[{"given":"Sanjai","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,7,19]]},"references-count":52,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0307600","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,19]]}}}