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Syphilis swept across the world in the 16th century as one of most prominent documented pandemics and is re-emerging worldwide despite the availability of effective antibiotics. Little is known about the genetic patterns in current infections or the evolutionary origins of the disease due to the non-cultivable and clonal nature of the causative bacterium Treponema pallidum subsp. pallidum. In this study, we used DNA capture and next generation sequencing to obtain whole genome data from syphilis patient specimens and from treponemes propagated in laboratory settings. Phylogenetic analyses indicate that the syphilis strains examined here share a common ancestor after the 15th century. Moreover, most contemporary strains are azithromycin resistant and members of a globally dominant cluster named here as SS14- Ω. This cluster diversified from a common ancestor in the mid-20th century and has the population genetic and epidemiological features indicative of the emergence of a pandemic strain cluster.

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