Ancient Bacterial Genomes Reveal a High Diversity of Treponema pallidum Strains in Early Modern Europe

Majander, Kerttu; Pfrengle, Saskia; Kocher, Arthur; Neukamm, Judith; Plessis, Louis du; Pla-Díaz, Marta; Arora, Natasha; Akgül, Gülfirde; Salo, Kati; Schats, Rachel; Inskip, Sarah; Oinonen, M.; Valk, Heiki; Malve, Martin; Крийска, Айвар; Onkamo, Päivi; Gónzález-Candelas, Fernando; Kühnert, Denise; Krause, Johannes; Schuenemann, Verena J.

doi:10.1016/j.cub.2020.07.058

Cited by 53 publications

(108 citation statements)

References 135 publications

(241 reference statements)

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“…We showed that TPE genomes in Maryland County form a monophyletic clade that is clearly distinct from other publicly available TPE genomes. The low genomic diversity within samples from Liberia is consistent with previous observations regarding low mutation rates of TPE and TPA (14,23) yet contrasts the genetic and geographic structuring observed in the broader global phylogeny. This finding suggests evolution and expansion of local TPE strains from a common ancestor subsequent to the benzathine penicillin-based eradication campaigns conducted until the 1960s, rather than recent importation from elsewhere.…”

Section: Discussionsupporting

confidence: 88%

“…Ancestral reconstruction on the phylogeny inferred that the maximum number of substitutions from the common ancestor of all genomes sequenced from Maryland County was 4. Contextualized by previous estimates that the molecular clock rate of T. pallidum is 4-9 years/substitutions/genome (14,23), which suggests a recent common ancestor within the past 16-36 years. Despite low overall diversity, there remained evidence of local geographic separation within Maryland County genomes, particularly among 2 northernmost communities ( Figure 3, clusters A, B).…”

Section: Reidentification Of Yaws Liberiamentioning

confidence: 92%

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Epidemiologic and Genomic Reidentification of Yaws, Liberia

Timothy¹,

Beale²,

Rogers³

et al. 2021

Emerg. Infect. Dis.

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We confirmed endemicity and autochthonous transmission of yaws in Liberia after a population-based, community-led burden estimation (56,825 participants). Serologically confirmed yaws was rare and focal at population level (24 cases; 2.6 [95% CI 1.4–3.9] cases/10,000 population) with similar clinical epidemiology to other endemic countries in West Africa. Unsupervised classification of spatially referenced case finding data indicated that yaws was more likely to occur in hard-to-reach communities; healthcare-seeking was low among communities, and clinical awareness of yaws was low among healthcare workers. We recovered whole bacterial genomes from 12 cases and describe a monophyletic clade of Treponema pallidum subspecies pertenue , phylogenetically distinct from known TPE lineages, including those affecting neighboring nonhuman primate populations (Taï Forest, Côte d’Ivoire). Yaws is endemic in Liberia but exhibits low focal population prevalence with evidence of a historical genetic bottleneck and subsequent local expansion. Reporting gaps appear attributable to challenging epidemiology and low disease awareness.

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Section: Discussionsupporting

confidence: 88%

Section: Reidentification Of Yaws Liberiamentioning

confidence: 92%

Epidemiologic and Genomic Reidentification of Yaws, Liberia

Timothy¹,

Beale²,

Rogers³

et al. 2021

Emerg. Infect. Dis.

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“…We excluded 8 samples from strains known to be heavily passaged or with uncertain collection dates from the previous dataset of 528, giving a dataset of 520 samples and 883 variable sites. We inferred a median molecular clock rate of 1.28 ×10 −7 substitutions/site/year (95% Highest Posterior Density (HPD) 1.07 ×10 −7 – 1.48 ×10 −7 ), equivalent to one substitution/genome every 6.9 years, consistent with recent analyses 4,6 .…”

Section: Resultssupporting

confidence: 83%

“…This filtered dataset comprised 401 new and 127 published genomes (Supplementary Data 1), but excluded the only sample from Belgium, leaving 22 countries in the analysis. After excluding 19 regions of recombination and genomic uncertainty due to gene orthology or repetitive regions 3,4,6 , we used Gubbins 26 to infer a further 19 regions of putative recombination (see Methods and Supplementary Data 2 for details). We refer to the resulting masked sequence alignment as the core genome and used it to infer a whole genome maximum likelihood phylogeny using IQ-Tree 27 (Supplementary Figure 2).…”

Section: Resultsmentioning

confidence: 99%

“…Historically, syphilis is commonly believed to have caused a large epidemic across Renaissance Europe, having previously been absent or unrecognised 1,2 . Although accurate dating of the most recent common ancestor of TPA is still the subject of debate 3–6 , it is suggested that the strains of TPA that persist in the human population to this day can be traced back to that introduction into Western Europe approximately 500 years ago, and subsequently disseminated globally 3,4,6 .…”

Section: Introductionmentioning

confidence: 99%

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Contemporary syphilis is characterised by rapid global spread of pandemicTreponema pallidumlineages

Beale

Marks

Cole

et al. 2021

Preprint

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Syphilis is an important sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum. The last two decades have seen syphilis incidence rise in many high-income countries, yet the evolutionary and epidemiological relationships that underpin this are poorly understood, as is the global T. pallidum population structure. We assembled a geographically and temporally diverse collection of clinical and laboratory samples comprising 726 T. pallidum genomes. We used detailed phylogenetic analysis and clustering to show that syphilis globally can be described by only two deeply branching lineages, Nichols and SS14. We show that both of these lineages can be found circulating concurrently in 12 of the 23 countries sampled. To provide further phylodynamic resolution we subdivided Treponema pallidum subspecies pallidum into 17 distinct sublineages. Importantly, like SS14, we provide evidence that two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analysis showed that recent isolates circulating in 14 different countries were genetically identical in their core genome to those from other countries, suggesting frequent exchange through international transmission pathways. This contrasts with the majority of samples collected prior to 1983, which are phylogenetically distinct from these more recently isolated sublineages. Bayesian temporal analysis provided evidence of a population bottleneck and decline occurring during the late 1990s, followed by a rapid population expansion a decade later. This was driven by the dominant T. pallidum sublineages circulating today, many of which are resistant to macrolides. Combined we show that the population of contemporary syphilis in high-income countries has undergone a recent and rapid global expansion.

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Paleopathology

Buikstra¹

2023

A Companion to Biological Anthropology

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Ancient Bacterial Genomes Reveal a High Diversity of Treponema pallidum Strains in Early Modern Europe

Cited by 53 publications

References 135 publications

Epidemiologic and Genomic Reidentification of Yaws, Liberia

Epidemiologic and Genomic Reidentification of Yaws, Liberia

Contemporary syphilis is characterised by rapid global spread of pandemicTreponema pallidumlineages

Paleopathology

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