Mass burial genomics reveals outbreak of enteric paratyphoid fever in the Late Medieval trade city Lübeck

Haller, Magdalena; Susat, Julian; Flux, Anna Lena; Immel, Alexander; Franke, André; Herbig, Alexander; Krause, Johannes; Kupczok, Anne; Fouquet, Gerhard; Hummel, Susanne; Rieger, Dirk; Nebel, Almut; Krause‐Kyora, Ben

doi:10.1016/j.isci.2021.102419

Cited by 13 publications

(32 citation statements)

References 41 publications

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“…The skeletal material analyzed in this study was excavated from four mass burials (contexts 4528, 4529, 4562 and 4571) located near the Heiligen-Geist-Hospital ("Hospital of the Holy Ghost", HGH) in Lübeck, northern Germany (8-10). The graves were dug between 1340 and 1370 CE (11).…”

Section: Methodsmentioning

confidence: 99%

“…We sampled almost exclusively teeth and used the whole specimens for aDNA extraction. The DNA was isolated with the BioRobot ® EZ1 Advanced applying a custom-made version of the Large-Volume-Protocol and the EZ1 DNA Investigator ® Kit (Qiagen) as described previously (11,30). The DNA extracts were then converted into indexed partial Uracil-DNA Glycosylase (UDG)treated libraries.…”

Section: Dna Extraction and Library Preparationmentioning

confidence: 99%

“…Molecular analysis of the human remains (1370 -1400 CE) indicated that individuals buried in the pits were infected with Salmonella enterica subsp. enterica serovar Paratyphi C at the time of death (11). The pathogen is a causative agent of paratyphoid fever, which is a lifethreatening illness transmitted through contaminated food and water (12).…”

Section: Introductionmentioning

confidence: 99%

“…Nowadays S. Paratyphi C is virtually absent in Europe, however, it can be assumed that the pathogen's prevalence used to be higher in the past. Discovery of S. Paratyphi C in medieval Germany (11) and Norway ( 13) suggests a change in the geographic distribution of Salmonella enterica species over time. It is thus possible that paratyphoid fever used to have a substantial impact on the health of Europeans at that time (11).…”

Section: Introductionmentioning

confidence: 99%

“…Discovery of S. Paratyphi C in medieval Germany (11) and Norway ( 13) suggests a change in the geographic distribution of Salmonella enterica species over time. It is thus possible that paratyphoid fever used to have a substantial impact on the health of Europeans at that time (11). As the pathogen's genome is thought to have been stable for millennia (13), genetic factors of the host could have contributed to the disappearance of this infectious disease in modern Europe.…”

Section: Introductionmentioning

confidence: 99%

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Ancient DNA Study in Medieval Europeans Shows an Association Between HLA-DRB1*03 and Paratyphoid Fever

Haller

Bonczarowska

Rieger³

et al. 2021

Front. Immunol.

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Outbreaks of infectious diseases repeatedly affected medieval Europe, leaving behind a large number of dead often inhumed in mass graves. Human remains interred in two burial pits from 14th century CE Germany exhibited molecular evidence of Salmonella enterica Paratyphi C (S. Paratyphi C) infection. The pathogen is responsible for paratyphoid fever, which was likely the cause of death for the buried individuals. This finding presented the unique opportunity to conduct a paratyphoid fever association study in a European population. We focused on HLA-DRB1*03:01 that is a known risk allele for enteric fever in present-day South Asians. We generated HLA profiles for 29 medieval S. Paratyphi C cases and 24 contemporaneous controls and compared these to a modern German population. The frequency of the risk allele was higher in the medieval cases (29.6%) compared to the contemporaneous controls (13%; p = 0.189), albeit not significantly so, possibly because of small sample sizes. Indeed, in comparison with the modern controls (n = 39,689; 10.2%; p = 0.005) the frequency difference became statistically significant. This comparison also suggested a slight decrease in the allele’s prevalence between the medieval and modern controls. Up to now, this is the first study on the genetic predisposition to Salmonella infection in Europeans and the only association analysis on paratyphoid fever C. Functional investigation using computational binding prediction between HLA variants and S. Paratyphi and S. Typhi peptides supported a reduced recognition capacity of bacterial proteins by DRB1*03:01 relative to other common DRB1 variants. This pattern could potentially explain the disease association. Our results suggest a slightly reduced predisposition to paratyphoid fever in modern Europeans. The causative allele, however, is still common today, which can be explained by a trade-off, as DRB1*03:01 is protective against infectious respiratory diseases such as severe respiratory syndrome (SARS). It is thus possible that the allele also provided resistance to corona-like viruses in the past.

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Section: Methodsmentioning

confidence: 99%

Section: Dna Extraction and Library Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ancient DNA Study in Medieval Europeans Shows an Association Between HLA-DRB1*03 and Paratyphoid Fever

Haller

Bonczarowska

Rieger³

et al. 2021

Front. Immunol.

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Ancient Yersinia pestis and Salmonella enterica genomes from Bronze Age Crete

et al. 2022

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Redefining the treponemal history through pre-Columbian genomes from Brazil

Majander,

Pla-Díaz,

du Plessis

et al. 2024

Nature

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The origins of treponemal diseases have long remained unknown, especially considering the sudden onset of the first syphilis epidemic in the late 15th century in Europe and its hypothesized arrival from the Americas with Columbus’ expeditions1,2. Recently, ancient DNA evidence has revealed various treponemal infections circulating in early modern Europe and colonial-era Mexico3–6. However, there has been to our knowledge no genomic evidence of treponematosis recovered from either the Americas or the Old World that can be reliably dated to the time before the first trans-Atlantic contacts. Here, we present treponemal genomes from nearly 2,000-year-old human remains from Brazil. We reconstruct four ancient genomes of a prehistoric treponemal pathogen, most closely related to the bejel-causing agent Treponema pallidum endemicum. Contradicting the modern day geographical niche of bejel in the arid regions of the world, the results call into question the previous palaeopathological characterization of treponeme subspecies and showcase their adaptive potential. A high-coverage genome is used to improve molecular clock date estimations, placing the divergence of modern T. pallidum subspecies firmly in pre-Columbian times. Overall, our study demonstrates the opportunities within archaeogenetics to uncover key events in pathogen evolution and emergence, paving the way to new hypotheses on the origin and spread of treponematoses.

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Mass burial genomics reveals outbreak of enteric paratyphoid fever in the Late Medieval trade city Lübeck

Abstract: Salmonella entericaParatyphi C detected in remains from a mass burial in Lü beck Outbreak of enteric paratyphoid fever likely occurred in 1367 CE Pathogen genomes showed close similarity to a strain from Norway (1200 CE)

Cited by 13 publications

References 41 publications

Ancient DNA Study in Medieval Europeans Shows an Association Between HLA-DRB1*03 and Paratyphoid Fever

Ancient DNA Study in Medieval Europeans Shows an Association Between HLA-DRB1*03 and Paratyphoid Fever

Ancient Yersinia pestis and Salmonella enterica genomes from Bronze Age Crete

Redefining the treponemal history through pre-Columbian genomes from Brazil

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