Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis

Mathew A. Beale*, Michael Marks, Michelle J. Cole, Min Kuang Lee, Rachel Pitt, Christopher Ruis, Eszter Balla, Tania Crucitti, Michael Ewens, Candela Fernández-Naval, Anna Grankvist, Malcolm Guiver, Chris R. Kenyon, Rafil Khairullin, Ranmini Kularatne, Maider Arando, Barbara J. Molini, Andrey Obukhov, Emma E. Page, Fruzsina PetrovayCornelis Rietmeijer, Dominic Rowley, Sandy Shokoples, Erasmus Smit, Emma L. Sweeney, George Taiaroa, Jaime H. Vera, Christine Wennerås, David M. Whiley, Deborah A. Williamson, Gwenda Hughes, Prenilla Naidu, Magnus Unemo, Mel Krajden, Sheila A. Lukehart, Muhammad G. Morshed, Helen Fifer, Nicholas R. Thomson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p.pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides.

Global syphilis prevalence has been increasing. Sequencing and analysis of a global collection of 726 Treponema pallidum samples reveal globally circulating lineages linked to a rapid expansion occurring since the end of the twentieth century.

Original languageEnglish
Pages (from-to)1549-1560
Number of pages12
JournalNature Microbiology
Issue number12
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
M.K. declares institutional funding from Roche, Hologic and Siemens, which is unrelated to this work. The remaining authors declare no competing interests. The funders had no input into the study design, interpretation or decision to submit for publication.

Funding Information:
We thank the sequencing team at the Wellcome Sanger Institute, and C. Puethe and the Pathogen Informatics team for computational support; additional technical staff involved in sample diagnostics, DNA extraction and sample retrieval in laboratories at Public Health England and NHS laboratories, UK; British Columbia CDC and Alberta Precision Laboratories, Canada; National Public Health Center, Budapest, Hungary; FRC Kazan Scientific Center, Tuva, Russia; National Institute for Communicable Diseases, Johannesburg, South Africa; Institute of Tropical Medicine, Antwerp, Belgium; Sahlgrenska University Hospital, Gothenburg, Sweden; Hospital Vall d’Hebron, Barcelona, Spain; Midlands Regional Hospital Portlaoise, Ireland; Pathology Queensland Central Laboratory, Australia; WHO Collaborating Centre for Gonorrhoea and other STIs, Sweden; G. Tonkin-Hill, A. van Tonder and members of the Thomson team for helpful discussions during analysis. M.A.B. and N.R.T. were supported by Wellcome funding to the Sanger Institute (#206194). M.M. was funded by the UKRI and NIHR (COV0335; MR/V027956/1, NIHR200125) and the EDCTP (RIA2018D-249). D.M.W. was funded by a Queensland Advancing Clinical Research Fellowship from the Queensland Government. D.A.W. was supported by an Investigator Grant (1174555) from the National Health and Medical Research Council of Australia. S.A.L. was funded by the National Institutes of Health (R01 AI42143 and R01 AI123196). This research was funded in whole, or in part, by the Wellcome Trust (#206194). For the purpose of open access, the authors have applied a CC-BY public copyright licence to any author-accepted manuscript version arising from this submission.

Publisher Copyright:
© 2021, The Author(s).


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