{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:49:32Z","timestamp":1791838172382,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010063","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000}}],"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"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":["U19AI144133"],"award-info":[{"award-number":["U19AI144133"]}],"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":["U19AI144133"],"award-info":[{"award-number":["U19AI144133"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["21K09388"],"award-info":[{"award-number":["21K09388"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21fk0108091j0303"],"award-info":[{"award-number":["21fk0108091j0303"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    In spite of its immutable susceptibility to penicillin,\n                    <jats:italic>Treponema pallidum<\/jats:italic>\n                    (\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>pallidum<\/jats:italic>\n                    ) subsp.\n                    <jats:italic>pallidum<\/jats:italic>\n                    continues to cause millions of cases of syphilis each year worldwide, resulting in significant morbidity and mortality and underscoring the urgency of developing an effective vaccine to curtail the spread of the infection. Several technical challenges, including absence of an\n                    <jats:italic>in vitro<\/jats:italic>\n                    culture system until very recently, have hampered efforts to catalog the diversity of strains collected worldwide. Here, we provide near-complete genomes from 196\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>pallidum<\/jats:italic>\n                    strains\u2013including 191\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>pallidum<\/jats:italic>\n                    subsp.\n                    <jats:italic>pallidum<\/jats:italic>\n                    \u2013sequenced directly from patient samples collected from 8 countries and 6 continents. Maximum likelihood phylogeny revealed that samples from most sites were predominantly SS14 clade. However, 99% (84\/85) of the samples from Madagascar formed two of the five distinct Nichols subclades. Although recombination was uncommon in the evolution of modern circulating strains, we found multiple putative recombination events between\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>pallidum<\/jats:italic>\n                    subsp.\n                    <jats:italic>pallidum<\/jats:italic>\n                    and subsp.\n                    <jats:italic>endemicum<\/jats:italic>\n                    , shaping the genomes of several subclades. Temporal analysis dated the most recent common ancestor of Nichols and SS14 clades to 1717 (95% HPD: 1543\u20131869), in agreement with other recent studies. Rates of SNP accumulation varied significantly among subclades, particularly among different Nichols subclades, and was associated in the Nichols A subclade with a C394F substitution in TP0380, a ERCC3-like DNA repair helicase. Our data highlight the role played by variation in genes encoding putative surface-exposed outer membrane proteins in defining separate lineages, and provide a critical resource for the design of broadly protective syphilis vaccines targeting surface antigens.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0010063","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T13:37:42Z","timestamp":1640180262000},"page":"e0010063","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":93,"title":["Treponema pallidum genome sequencing from six continents reveals variability in vaccine candidate genes and dominance of Nichols clade strains in Madagascar"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9334-8150","authenticated-orcid":true,"given":"Nicole A. P.","family":"Lieberman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6925-9948","authenticated-orcid":true,"given":"Michelle J.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6610-0723","authenticated-orcid":true,"given":"Hong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasata","family":"Shrestha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meei-Li","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9122-9211","authenticated-orcid":true,"given":"Austin M.","family":"Haynes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7295-9531","authenticated-orcid":true,"given":"Emily","family":"Romeis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Qiu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3757-5441","authenticated-orcid":true,"given":"Cai-Xia","family":"Kou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Ciccarese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivano","family":"Dal Conte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4757-6798","authenticated-orcid":true,"given":"Marco","family":"Cusini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Drago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1495-0926","authenticated-orcid":true,"given":"Shu-ichi","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4765-0989","authenticated-orcid":true,"given":"Kenichi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Ohnishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-0174","authenticated-orcid":true,"given":"Kelika A.","family":"Konda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silver K.","family":"Vargas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Eguiluz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos F.","family":"Caceres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey D.","family":"Klausner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriol","family":"Mitj\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6398-9061","authenticated-orcid":true,"given":"Anne","family":"Rompalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Mulcahy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward W.","family":"Hook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9778-3301","authenticated-orcid":true,"given":"Sheila A.","family":"Lukehart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-8578","authenticated-orcid":true,"given":"Amanda M.","family":"Casto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavitra","family":"Roychoudhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"DiMaio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Giacani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-0527","authenticated-orcid":true,"given":"Alexander L.","family":"Greninger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"pntd.0010063.ref001","first-page":"1178633719883282","article-title":"Resurgence of Syphilis in the United States: An Assessment of Contributing Factors","volume":"12","author":"R Schmidt","year":"2019","journal-title":"Infect Dis"},{"key":"pntd.0010063.ref002","unstructured":"U.S. Department of Health & Human Services. National Overview\u2014Sexually Transmitted Disease Surveillance, 2019. [cited 19 Apr 2021]. Available: https:\/\/www.cdc.gov\/std\/statistics\/2019\/overview.htm#Syphilis"},{"key":"pntd.0010063.ref003","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s40471-018-0138-z","article-title":"An Update on the Global Epidemiology of Syphilis","volume":"5","author":"N Kojima","year":"2018","journal-title":"Curr Epidemiol Rep"},{"key":"pntd.0010063.ref004","doi-asserted-by":"crossref","first-page":"e0198622","DOI":"10.1371\/journal.pone.0198622","article-title":"Gaps in the implementation of antenatal syphilis detection and treatment in health facilities across sub-Saharan Africa.","volume":"13","author":"M Kanyangarara","year":"2018","journal-title":"PloS One."},{"key":"pntd.0010063.ref005","doi-asserted-by":"crossref","first-page":"e0211720","DOI":"10.1371\/journal.pone.0211720","article-title":"Global burden of maternal and congenital syphilis and associated adverse birth outcomes-Estimates for 2016 and progress since 2012","volume":"14","author":"EL Korenromp","year":"2019","journal-title":"PloS One."},{"key":"pntd.0010063.ref006","doi-asserted-by":"crossref","first-page":"e1002473","DOI":"10.1371\/journal.pmed.1002473","article-title":"Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis: An evaluation from multi-country surveys and stakeholder interviews","volume":"14","author":"S Nurse-Findlay","year":"2017","journal-title":"PLoS Med"},{"key":"pntd.0010063.ref007","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1128\/AAC.44.3.806-807.2000","article-title":"A point mutation associated with bacterial macrolide resistance is present in both 23S rRNA genes of an erythromycin-resistant Treponema pallidum clinical isolate","volume":"44","author":"LV Stamm","year":"2000","journal-title":"Antimicrob Agents Chemother"},{"key":"pntd.0010063.ref008","doi-asserted-by":"crossref","first-page":"678","DOI":"10.4269\/ajtmh.15-0316","article-title":"Macrolide Resistance in the Syphilis Spirochete, Treponema pallidum ssp. pallidum: Can We Also Expect Macrolide-Resistant Yaws Strains?","volume":"93","author":"D \u0160majs","year":"2015","journal-title":"Am J Trop Med Hyg"},{"key":"pntd.0010063.ref009","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1086\/509512","article-title":"Antibiotic selection may contribute to increases in macrolide-resistant Treponema pallidum","volume":"194","author":"CM Marra","year":"2006","journal-title":"J Infect Dis"},{"key":"pntd.0010063.ref010","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.1128\/jb.171.9.5005-5011.1989","article-title":"Demonstration of rare protein in the outer membrane of Treponema pallidum subsp. pallidum by freeze-fracture analysis","volume":"171","author":"EM Walker","year":"1989","journal-title":"J Bacteriol"},{"key":"pntd.0010063.ref011","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1111\/j.1365-2958.1995.tb02332.x","article-title":"Treponema pallidum and the quest for outer membrane proteins","volume":"16","author":"JD Radolf","year":"1995","journal-title":"Mol Microbiol"},{"key":"pntd.0010063.ref012","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1128\/IAI.00360-15","article-title":"Transcription of TP0126, Treponema pallidum putative OmpW homolog, is regulated by the length of a homopolymeric guanosine repeat","volume":"83","author":"L Giacani","year":"2015","journal-title":"Infect Immun"},{"key":"pntd.0010063.ref013","doi-asserted-by":"crossref","first-page":"e0008812","DOI":"10.1371\/journal.pntd.0008812","article-title":"Transcriptional and immunological analysis of the putative outer membrane protein and vaccine candidate TprL of Treponema pallidum","volume":"15","author":"AM Haynes","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010063.ref014","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1111\/j.1365-2958.2004.04086.x","article-title":"Gene conversion: a mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection","volume":"52","author":"A Centurion-Lara","year":"2004","journal-title":"Mol Microbiol"},{"key":"pntd.0010063.ref015","first-page":"3822","article-title":"Antigenic variation in Treponema pallidum: TprK sequence diversity accumulates in response to immune pressure during experimental syphilis","volume":"184","author":"L Giacani","year":"2010","journal-title":"J Immunol Baltim Md 1950"},{"key":"pntd.0010063.ref016","doi-asserted-by":"crossref","first-page":"4959","DOI":"10.1128\/IAI.02236-14","article-title":"Antigenic variation of TprK facilitates development of secondary syphilis","volume":"82","author":"TB Reid","year":"2014","journal-title":"Infect Immun"},{"key":"pntd.0010063.ref017","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01153-18","article-title":"Long-Term In Vitro Culture of the Syphilis Spirochete Treponema pallidum subsp. pallidum","volume":"9","author":"DG Edmondson","year":"2018","journal-title":"mBio"},{"key":"pntd.0010063.ref018","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1097\/01.OLQ.0000123653.84940.59","article-title":"Resurgence in Infectious Syphilis in Ireland: An Epidemiological Study.","volume":"31","author":"S Hopkins","year":"2004","journal-title":"Sex Transm Dis"},{"key":"pntd.0010063.ref019","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1056\/NEJMoa040216","article-title":"Macrolide resistance in Treponema pallidum in the United States and Ireland","volume":"351","author":"SA Lukehart","year":"2004","journal-title":"N Engl J Med"},{"key":"pntd.0010063.ref020","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1086\/656533","article-title":"Enhanced molecular typing of treponema pallidum: geographical distribution of strain types and association with neurosyphilis","volume":"202","author":"CM Marra","year":"2010","journal-title":"J Infect Dis"},{"key":"pntd.0010063.ref021","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1086\/652239","article-title":"A Phase III Equivalence Trial of Azithromycin versus Benzathine Penicillin for Treatment of Early Syphilis","volume":"201","author":"EW Hook","year":"2010","journal-title":"J Infect Dis"},{"key":"pntd.0010063.ref022","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1097\/OLQ.0b013e3181bd11dd","article-title":"Evaluation of Azithromycin Resistance in Treponema pallidum Specimens From Madagascar","volume":"36","author":"K Van Damme","year":"2009","journal-title":"Sex Transm Dis"},{"key":"pntd.0010063.ref023","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"},{"key":"pntd.0010063.ref024","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"},{"key":"pntd.0010063.ref025","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1097\/OLQ.0b013e31826ae7a8","article-title":"Two mutations associated with macrolide resistance in Treponema pallidum: increasing prevalence and correlation with molecular strain type in Seattle, Washington","volume":"39","author":"M Grimes","year":"2012","journal-title":"Sex Transm Dis"},{"key":"pntd.0010063.ref026","doi-asserted-by":"crossref","first-page":"16190","DOI":"10.1038\/nmicrobiol.2016.190","article-title":"Genome-scale analysis of the non-cultivable Treponema pallidum reveals extensive within-patient genetic variation","volume":"2","author":"M Pinto","year":"2016","journal-title":"Nat Microbiol"},{"key":"pntd.0010063.ref027","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.1038\/s41598-021-82337-7","article-title":"Phylogenetic and genetic characterization of Treponema pallidum strains from syphilis patients in Japan by whole-genome sequence analysis from global perspectives","volume":"11","author":"S Nishiki","year":"2021","journal-title":"Sci Rep"},{"key":"pntd.0010063.ref028","doi-asserted-by":"crossref","first-page":"e1832","DOI":"10.1371\/journal.pntd.0001832","article-title":"Whole genome sequence of Treponema pallidum ssp. pallidum, strain Mexico A, suggests recombination between yaws and syphilis strains.","volume":"6","author":"H P\u011btro\u0161ov\u00e1","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010063.ref029","doi-asserted-by":"crossref","first-page":"e2222","DOI":"10.1371\/journal.pntd.0002222","article-title":"Fine analysis of genetic diversity of the tpr gene family among treponemal species, subspecies and strains","volume":"7","author":"A Centurion-Lara","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010063.ref030","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01006-18","article-title":"Sequence Variation of Rare Outer Membrane Protein \u03b2-Barrel Domains in Clinical Strains Provides Insights into the Evolution of Treponema pallidum subsp. pallidum, the Syphilis Spirochete","volume":"9","author":"S Kumar","year":"2018","journal-title":"mBio"},{"key":"pntd.0010063.ref031","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.3201\/eid2508.181690","article-title":"Bejel, a Nonvenereal Treponematosis, among Men Who Have Sex with Men, Japan","volume":"25","author":"T Kawahata","year":"2019","journal-title":"Emerg Infect Dis"},{"key":"pntd.0010063.ref032","first-page":"1210.e1","article-title":"Bejel in Cuba: molecular identification of Treponema pallidum subsp. endemicum in patients diagnosed with venereal syphilis","volume":"24","author":"AA Noda","year":"2018","journal-title":"Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis"},{"key":"pntd.0010063.ref033","doi-asserted-by":"crossref","first-page":"e0005434","DOI":"10.1371\/journal.pntd.0005434","article-title":"Human Treponema pallidum 11q\/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively","volume":"11","author":"L Mikalov\u00e1","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010063.ref034","doi-asserted-by":"crossref","first-page":"e6182","DOI":"10.7717\/peerj.6182","article-title":"A public database for the new MLST scheme for Treponema pallidum subsp. pallidum: surveillance and epidemiology of the causative agent of syphilis","volume":"6","author":"L Grillova","year":"2019","journal-title":"PeerJ"},{"key":"pntd.0010063.ref035","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.3389\/fmicb.2019.01691","article-title":"Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens","volume":"10","author":"L Grillov\u00e1","year":"2019","journal-title":"Front Microbiol"},{"key":"pntd.0010063.ref036","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1093\/molbev\/msl092","article-title":"Molecular evolution of the tprC, D, I, K, G, and J genes in the pathogenic genus Treponema","volume":"23","author":"RR Gray","year":"2006","journal-title":"Mol Biol Evol"},{"key":"pntd.0010063.ref037","doi-asserted-by":"crossref","first-page":"3788","DOI":"10.1016\/j.cub.2020.07.058","article-title":"Ancient Bacterial Genomes Reveal a High Diversity of Treponema pallidum Strains in Early Modern Europe","volume":"30","author":"K Majander","year":"2020","journal-title":"Curr Biol CB"},{"key":"pntd.0010063.ref038","doi-asserted-by":"crossref","first-page":"e2172","DOI":"10.1371\/journal.pntd.0002172","article-title":"Whole genome sequence of the Treponema Fribourg-Blanc: unspecified simian isolate is highly similar to the yaws subspecies","volume":"7","author":"M Zoban\u00edkov\u00e1","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010063.ref039","doi-asserted-by":"crossref","first-page":"e1006650","DOI":"10.1371\/journal.pcbi.1006650","article-title":"BEAST 2.5: An advanced software platform for Bayesian evolutionary analysis","volume":"15","author":"R Bouckaert","year":"2019","journal-title":"PLoS Comput Biol"},{"key":"pntd.0010063.ref040","doi-asserted-by":"crossref","first-page":"16245","DOI":"10.1038\/nmicrobiol.2016.245","article-title":"Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster","volume":"2","author":"N Arora","year":"2017","journal-title":"Nat Microbiol"},{"key":"pntd.0010063.ref041","doi-asserted-by":"crossref","first-page":"e0202619","DOI":"10.1371\/journal.pone.0202619","article-title":"Sequencing of Treponema pallidum subsp. pallidum from isolate UZ1974 using Anti-Treponemal Antibodies Enrichment: First complete whole genome sequence obtained directly from human clinical material","volume":"13","author":"L Grillov\u00e1","year":"2018","journal-title":"PloS One"},{"key":"pntd.0010063.ref042","doi-asserted-by":"crossref","first-page":"e0005894","DOI":"10.1371\/journal.pntd.0005894","article-title":"Complete genome sequences of two strains of Treponema pallidum subsp. pertenue from Ghana, Africa: Identical genome sequences in samples isolated more than 7 years apart","volume":"11","author":"M Strouhal","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010063.ref043","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.21105\/joss.02906","article-title":"Augur: a bioinformatics toolkit for phylogenetic analyses of human pathogens","volume":"6","author":"J Huddleston","year":"2021","journal-title":"J Open Source Softw"},{"key":"pntd.0010063.ref044","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12900-018-0086-3","article-title":"Functional insights from proteome-wide structural modeling of Treponema pallidum subspecies pallidum, the causative agent of syphilis","volume":"18","author":"S Houston","year":"2018","journal-title":"BMC Struct Biol"},{"key":"pntd.0010063.ref045","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1128\/JCM.44.3.888-891.2006","article-title":"Reactivity of antibodies from syphilis patients to a protein array representing the Treponema pallidum proteome","volume":"44","author":"MB Brinkman","year":"2006","journal-title":"J Clin Microbiol"},{"key":"pntd.0010063.ref046","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1128\/IAI.00173-10","article-title":"Characterization and serologic analysis of the Treponema pallidum proteome","volume":"78","author":"MA McGill","year":"2010","journal-title":"Infect Immun"},{"key":"pntd.0010063.ref047","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1128\/IAI.68.3.1633-1648.2000","article-title":"Comparative genome analysis of the pathogenic spirochetes Borrelia burgdorferi and Treponema pallidum","volume":"68","author":"G Subramanian","year":"2000","journal-title":"Infect Immun"},{"key":"pntd.0010063.ref048","article-title":"Structural modeling of the Treponema pallidum OMPeome: a roadmap for deconvolution of syphilis pathogenesis and development of a syphilis vaccine","author":"KL Hawley","year":"2021","journal-title":"J Bacteriol"},{"key":"pntd.0010063.ref049","first-page":"1","article-title":"The Treponema pallidum Outer Membrane","volume":"415","author":"JD Radolf","year":"2018","journal-title":"Curr Top Microbiol Immunol"},{"key":"pntd.0010063.ref050","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1128\/IAI.01424-07","article-title":"A novel Treponema pallidum antigen, TP0136, is an outer membrane protein that binds human fibronectin","volume":"76","author":"MB Brinkman","year":"2008","journal-title":"Infect Immun"},{"key":"pntd.0010063.ref051","doi-asserted-by":"crossref","first-page":"e0007401","DOI":"10.1371\/journal.pntd.0007401","article-title":"Analysis of host cell binding specificity mediated by the Tp0136 adhesin of the syphilis agent Treponema pallidum subsp. pallidum","volume":"13","author":"V Djokic","year":"2019","journal-title":"PLoS Negl Trop Dis."},{"key":"pntd.0010063.ref052","doi-asserted-by":"crossref","first-page":"e0003662","DOI":"10.1371\/journal.pntd.0003662","article-title":"Treponema pallidum subsp. pallidum TP0136 Protein Is Heterogeneous among Isolates and Binds Cellular and Plasma Fibronectin via its NH2-Terminal End","volume":"9","author":"W Ke","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0010063.ref053","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"},{"key":"pntd.0010063.ref054","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.4161\/hv.7.10.16541","article-title":"Enhanced immune response and protective efficacy of a Treponema pallidum Tp92 DNA vaccine vectored by chitosan nanoparticles and adjuvanted with IL-2.","volume":"7","author":"F Zhao","year":"2011","journal-title":"Hum Vaccin"},{"key":"pntd.0010063.ref055","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.micinf.2007.05.018","article-title":"Assessment of cell-surface exposure and vaccinogenic potentials of Treponema pallidum candidate outer membrane proteins","volume":"9","author":"FL Tomson","year":"2007","journal-title":"Microbes Infect"},{"key":"pntd.0010063.ref056","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1016\/j.jmb.2017.12.007","article-title":"A Completely Reimplemented MPI Bioinformatics Toolkit with a New HHpred Server at its Core","volume":"430","author":"L Zimmermann","year":"2018","journal-title":"J Mol Biol"},{"key":"pntd.0010063.ref057","doi-asserted-by":"crossref","DOI":"10.1002\/cpbi.108","article-title":"Protein Sequence Analysis Using the MPI Bioinformatics Toolkit","volume":"72","author":"F Gabler","year":"2020","journal-title":"Curr Protoc Bioinforma"},{"key":"pntd.0010063.ref058","doi-asserted-by":"crossref","first-page":"W244","DOI":"10.1093\/nar\/gki408","article-title":"The HHpred interactive server for protein homology detection and structure prediction","volume":"33","author":"J S\u00f6ding","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"pntd.0010063.ref059","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1016\/j.str.2013.08.005","article-title":"High-Resolution Comparative Modeling with RosettaCM","volume":"21","author":"Y Song","year":"2013","journal-title":"Structure"},{"key":"pntd.0010063.ref060","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1111\/j.1365-2958.2011.07662.x","article-title":"TP0326, a Treponema pallidum \u03b2-barrel assembly machinery A (BamA) orthologue and rare outer membrane protein","volume":"80","author":"DC Desrosiers","year":"2011","journal-title":"Mol Microbiol"},{"key":"pntd.0010063.ref061","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41587-019-0036-z","article-title":"SignalP 5.0 improves signal peptide predictions using deep neural networks","volume":"37","author":"JJ Almagro Armenteros","year":"2019","journal-title":"Nat Biotechnol"},{"key":"pntd.0010063.ref062","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"},{"key":"pntd.0010063.ref063","doi-asserted-by":"crossref","first-page":"W24","DOI":"10.1093\/nar\/gkx346","article-title":"BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes","volume":"45","author":"MC Jespersen","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"pntd.0010063.ref064","doi-asserted-by":"crossref","first-page":"e25069","DOI":"10.1371\/journal.pone.0025069","article-title":"Conservation of the human integrin-type beta-propeller domain in bacteria","volume":"6","author":"B Chouhan","year":"2011","journal-title":"PloS One."},{"key":"pntd.0010063.ref065","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.str.2019.02.002","article-title":"Architecture and Evolution of Blade Assembly in \u03b2-propeller Lectins","volume":"27","author":"F Bonnardel","year":"2019","journal-title":"Structure"},{"key":"pntd.0010063.ref066","article-title":"Contemporary syphilis is characterised by rapid global spread of pandemic Treponema pallidum lineages.","author":"MA Beale","year":"2021","journal-title":"Infectious Diseases (except HIV\/AIDS)"},{"key":"pntd.0010063.ref067","doi-asserted-by":"crossref","first-page":"e0238520","DOI":"10.1128\/JCM.02385-20","article-title":"Treponema pallidum Macrolide Resistance and Molecular Epidemiology in Southern Africa, 2008 to 2018","volume":"59","author":"JME Venter","year":"2021","journal-title":"J Clin Microbiol"},{"key":"pntd.0010063.ref068","doi-asserted-by":"crossref","first-page":"e2292","DOI":"10.1371\/journal.pone.0002292","article-title":"The binary protein interactome of Treponema pallidum\u2014the syphilis spirochete","volume":"3","author":"B Titz","year":"2008","journal-title":"PloS One"},{"key":"pntd.0010063.ref069","article-title":"Genetic Engineering of Treponema pallidum subsp. pallidum, the Syphilis Spirochete","author":"E Romeis","year":"2021","journal-title":"Microbiology"},{"key":"pntd.0010063.ref070","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02726-20","article-title":"Estimation of Full-Length TprK Diversity in Treponema pallidum subsp. pallidum","volume":"11","author":"A Addetia","year":"2020","journal-title":"mBio"},{"key":"pntd.0010063.ref071","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":"Bioinforma Oxf Engl"},{"key":"pntd.0010063.ref072","author":"B. Bushnell","journal-title":"BBMap short read aligner, and other bioinformatic tools"},{"key":"pntd.0010063.ref073","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"B Langmead","year":"2012","journal-title":"Nat Methods"},{"key":"pntd.0010063.ref074","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"key":"pntd.0010063.ref075","unstructured":"Broad Institute. Picard. Available: http:\/\/broadinstitute.github.io\/picard."},{"key":"pntd.0010063.ref076","doi-asserted-by":"crossref","first-page":"e1005595","DOI":"10.1371\/journal.pcbi.1005595","article-title":"Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads","volume":"13","author":"RR Wick","year":"2017","journal-title":"PLOS Comput Biol"},{"key":"pntd.0010063.ref077","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinforma Oxf Engl"},{"key":"pntd.0010063.ref078","doi-asserted-by":"crossref","DOI":"10.1128\/mSphereDirect.00283-18","article-title":"Ultrasensitive Capture of Human Herpes Simplex Virus Genomes Directly from Clinical Samples Reveals Extraordinarily Limited Evolution in Cell Culture","volume":"3","author":"AL Greninger","year":"2018","journal-title":"mSphere"},{"key":"pntd.0010063.ref079","doi-asserted-by":"crossref","first-page":"e112963","DOI":"10.1371\/journal.pone.0112963","article-title":"Pilon: An Integrated Tool for Comprehensive Microbial Variant Detection and Genome Assembly Improvement","volume":"9","author":"BJ Walker","year":"2014","journal-title":"PLoS ONE"},{"key":"pntd.0010063.ref080","unstructured":"Geneious. Geneious. Available: https:\/\/www.geneious.com"},{"key":"pntd.0010063.ref081","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"},{"key":"pntd.0010063.ref082","unstructured":"Kwong J, Seemann T. maskrc-svg. Available: https:\/\/github.com\/kwongj\/maskrc-svg"},{"key":"pntd.0010063.ref083","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1093\/molbev\/msu300","article-title":"IQ-TREE: A Fast and Effective Stochastic Algorithm for Estimating Maximum-Likelihood Phylogenies","volume":"32","author":"L-T Nguyen","year":"2015","journal-title":"Mol Biol Evol"},{"key":"pntd.0010063.ref084","doi-asserted-by":"crossref","first-page":"vew007","DOI":"10.1093\/ve\/vew007","article-title":"Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen).","volume":"2","author":"A Rambaut","year":"2016","journal-title":"Virus Evol."},{"key":"pntd.0010063.ref085","unstructured":"Pages H, Aboyoun P, Gentleman R, DebRoy S. Biostrings: Efficient manipulation of biological strings. R package version 2.60.1. Available: https:\/\/bioconductor.org\/packages\/Biostrings"},{"key":"pntd.0010063.ref086","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1093\/bioinformatics\/btu153","article-title":"Prokka: rapid prokaryotic genome annotation","volume":"30","author":"T. Seemann","year":"2014","journal-title":"Bioinforma Oxf Engl"},{"key":"pntd.0010063.ref087","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/2041-210X.12628","article-title":"ggtree: an R package for visualization and annotation of phylogenetic trees with their covariates and other associated data","volume":"8","author":"G Yu","year":"2017","journal-title":"Methods Ecol Evol"},{"key":"pntd.0010063.ref088","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/molbev\/msz240","article-title":"Treeio: An R Package for Phylogenetic Tree Input and Output with Richly Annotated and Associated Data. Kumar S, editor","volume":"37","author":"L-G Wang","year":"2020","journal-title":"Mol Biol Evol"},{"key":"pntd.0010063.ref089","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"H. Wickham","year":"2016","edition":"2"},{"key":"pntd.0010063.ref090","unstructured":"Yu G, Zhou L, Xu S, Huang H. In: ggmsa 1.0.0 [Internet]. [cited 11 Jul 2021]. Available: http:\/\/yulab-smu.top\/ggmsa\/authors.html"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0010063","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T20:56:13Z","timestamp":1674161773000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010063"}},"subtitle":[],"editor":[{"given":"Brian","family":"Stevenson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,22]]},"references-count":90,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0010063","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.08.17.456619","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,22]]}}}