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However, research on the genomic features of the <jats:italic>Treponema pallidum<\/jats:italic> subspecies <jats:italic>pallidum<\/jats:italic> (TPA) strains from these cases has been limited. Here, we elucidated the genetic variations and relationships between TPA strains in Japan (detected between 2014 and 2018) and other countries by whole-genome sequencing and phylogenetic analyses, including syphilis epidemiological surveillance data and information on patient sexual orientation. Seventeen of the 20 strains in Japan were SS14- and the remaining 3 were Nichols-lineage. Sixteen of the 17 SS14-lineage strains were classified into previously reported Sub-lineage 1B. Sub-lineage 1B strains in Japan have formed distinct sub-clusters of strains from heterosexuals and strains from men who have sex with men. These strains were closely related to reported TPA strains in China, forming an East-Asian cluster. However, those strains in these countries evolved independently after diverging from their most recent common ancestor and expanded their genetic diversity during the time of syphilis outbreak in each country. The genetic difference between the TPA strains in these countries was characterized by single-nucleotide-polymorphism analyses of their penicillin binding protein genes. Taken together, our results elucidated the detailed phylogenetic features and transmission networks of syphilis.<\/jats:p>","DOI":"10.1038\/s41598-021-82337-7","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T11:25:08Z","timestamp":1612437908000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Phylogenetic and genetic characterization of Treponema pallidum strains from syphilis patients in Japan by whole-genome sequence analysis from global perspectives"],"prefix":"10.1038","volume":"11","author":[{"given":"Shingo","family":"Nishiki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizue","family":"Kanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-ichi","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Ohnishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"82337_CR1","doi-asserted-by":"publisher","first-page":"e0143304","DOI":"10.1371\/journal.pone.0143304","volume":"10","author":"L Newman","year":"2015","unstructured":"Newman, L. et al. Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS ONE 10, e0143304 (2015).","journal-title":"PLoS ONE"},{"key":"82337_CR2","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/S1473-3099(08)70065-3","volume":"8","author":"KA Fenton","year":"2008","unstructured":"Fenton, K. A. et al. Infectious syphilis in high-income settings in the 21st century. Lancet Infect. Dis. 8, 244\u2013253 (2008).","journal-title":"Lancet Infect. Dis."},{"key":"82337_CR3","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1097\/OLQ.0000000000000768","volume":"45","author":"T Takahashi","year":"2018","unstructured":"Takahashi, T. et al. Rapid increase in reports of syphilis associated with men who have sex with women and women who have sex with men, Japan, 2012 to 2016. Sex. Transm. Dis. 45, 139\u2013143 (2018).","journal-title":"Sex. Transm. 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Syphilis testing, typing, and treatment follow-up: A new era for an old disease. Curr. Opin. Infect. Dis. 28, 53\u201360 (2015).","journal-title":"Curr. Opin. Infect. Dis."},{"key":"82337_CR7","doi-asserted-by":"publisher","first-page":"e74319","DOI":"10.1371\/journal.pone.0074319","volume":"8","author":"H P\u011btro\u0161ov\u00e1","year":"2013","unstructured":"P\u011btro\u0161ov\u00e1, H. et al. Resequencing of Treponema pallidum ssp. pallidum strains Nichols and SS14: Correction of sequencing errors resulted in increased separation of syphilis treponeme subclusters. PLoS ONE 8, e74319 (2013).","journal-title":"PLoS ONE"},{"key":"82337_CR8","doi-asserted-by":"publisher","first-page":"e0182768","DOI":"10.1371\/journal.pone.0182768","volume":"12","author":"ML Tong","year":"2017","unstructured":"Tong, M. L. et al. Whole genome sequence of the Treponema pallidum subsp. pallidum strain Amoy: An Asian isolate highly similar to SS14. PLoS ONE 12, e0182768 (2017).","journal-title":"PLoS ONE"},{"key":"82337_CR9","doi-asserted-by":"publisher","first-page":"42904","DOI":"10.18632\/oncotarget.10154","volume":"7","author":"J Sun","year":"2016","unstructured":"Sun, J. et al. Tracing the origin of Treponema pallidum in China using next-generation sequencing. Oncotarget 7, 42904\u201342918 (2016).","journal-title":"Oncotarget"},{"key":"82337_CR10","doi-asserted-by":"publisher","first-page":"16245","DOI":"10.1038\/nmicrobiol.2016.245","volume":"2","author":"N Arora","year":"2016","unstructured":"Arora, N. et al. Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster. Nat. Microbiol. 2, 16245 (2016).","journal-title":"Nat. Microbiol."},{"key":"82337_CR11","doi-asserted-by":"publisher","first-page":"3255","DOI":"10.1038\/s41467-019-11216-7","volume":"10","author":"MA Beale","year":"2019","unstructured":"Beale, M. A. et al. 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Dis."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82337-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82337-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82337-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T03:05:04Z","timestamp":1670036704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-82337-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,4]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["82337"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-82337-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,4]]},"assertion":[{"value":"21 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3154"}}