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EvolTB

Aufklärung der Entwicklungsgeschichte des Mycobacterium tuberculosis complex (MTBC)

Bis heute ist Tuberkulose eine der zehn häufigsten Todesursachen weltweit. Neuere Ansätze zur Eindämmung der Ausbreitung dieser Krankheit scheitern häufig an dem Unwissen über die evolutionäre Vergangenheit ihres Erregers Mycobacterium tuberculosis. Skelettveränderungen an antiken menschlichen Überresten beweisen, dass Tuberkulose seit mehreren tausend Jahren eine Geißel der Menschheit ist. Untersuchungen auf molekularer Ebene sind jedoch weiterhin schwierig, da die Proben schlecht konserviert sind und durch die Umwelt stark kontaminiert sind.

In diesem Projekt wollen wir mithilfe eines interdisziplinären Ansatzes antike Genome des Mycobacterium tuberculosis Komplex (MTBC) rekonstruieren. Zunächst möchten wir eine Anreicherungstechnik optimieren, die auf MTBC-spezifische DNA abzielt. Als nächstes werden wir hochauflösende alte Genomdaten durch Next-Generation Sequenzierung produzieren und bioinformatische Methoden anwenden, um den Beginn und die Entwicklung dieses Pathogens zu verstehen.

Project duration: October 2018 - September 2022
Project status:
Funding:
Internal funding EURAC (Project)
Institute: Institut für Mumienforschung

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Paläopathologie Mumien Genetik

Scientific Publications

Journal article2024

Histology of pulmonary tuberculosis in a 19th-century mummy from Comiso (Sicily, Italy)

Gaeta R, Giuffra V, Maixner F, Aringhieri G, Fornaciari A

Frank Maixner

Objective: The aim of this study is to investigate potential evidence of tuberculosis in mummified remains.

Materials: The natural mummy of an anonymous friar from the mortuary chapel of the church of Santa Maria della Grazia in Comiso (Sicily)

Methods: The mummy was studied through macroscopic examination; tissue sampling was conducted through breaches in the dorsal surface of the thorax. Radiological, histological and immunohistochemical analyses were performed on the pulmonary parenchyma.

Results: The mummified remains are those of an adult male approximately 25–45 years old. In the left lung, 7 intra parenchymal calcified nodules were detected. The fibrocalcific nodules showed some lacunae surrounded by fibrous tissue containing amorphous necrotic, most probably caseous, material.

Conclusions: These findings are compatible with a chronic infectious-inflammatory disease, likely a calcification of a previous Ghon complex of an apical nodular tuberculosis.

Significance: Our study supports the great spread of the disease in the 19th century; a time when it reached its maximum peak in Europe.

Limitations: Molecular investigations failed to detect traces of Mycobacterium tuberculosis DNA in the sample.

Suggestions for further research: The investigation on the mummies from Comiso is still in progress, and further analyses will potentially provide paleopathological data on this community of Modern Age which could be in tegrated with historical and archival sources.

DOI

DOI: 10.1016/j.ijpp.2024.11.001

Journal article2023

Hit or miss: A metagenomic evaluation of intra-bone variability of host pathogen load in tuberculosis-infected human remains

Jäger HY, Atz Zanotelli D, Maixner F, Nicklisch N, Alt KW, Meller H, Pap I, Szikossy I,

Frank Maixner, Albert Zink

Many sampling protocols have been established to successfully retrieve human DNA from archaeological remains, however the systematic detection of ancient pathogens remains challenging. Here, we present a first assessment of the intra-bone variability of metagenomic composition in human skeletal remains and its effect on the sampling success for Mycobacterium tuberculosis (MTB) and human endogenous DNA. For this purpose, four bone samples from published peer-reviewed studies with PCR-based evidence for ancient MTB DNA were selected. Two bone samples of a Neolithic individual from Halberstadt, Germany and two ribs of two 18th-century Hungarian church mummies were sampled at multiple locations for equal amounts, followed by DNA extraction and library construction. Shotgun sequencing data was generated for taxonomic profiling as well as quantitative and qualitative evaluation of MTB and human endogenous DNA. Despite low variance in microbial diversity within and across samples, intra-bone variability of up to 36.45- and 62.88-fold for authentic ancient MTB and human reads, respectively, was detected. This study demonstrates the variable sampling success for MTB and human endogenous DNA within single skeletal samples despite relatively consistent microbial composition and highlights how a multisampling approach can facilitate the detection of hotspots with highly concentrated pathogen and human endogenous DNA.

DOI

DOI: 10.1016/j.tube.2023.102392

Journal article2023

Paleopathology and evolution of tuberculosis editorial

Pálfi G, Dutour O, Hajdu T, Sola C, Zink A

Albert Zink

Part of special issue
Supplement Issue: Paleopathology and Evolution of Tuberculosis: Conference Proceedings from the 3rd International Congress on the Evolution and Paleoepidemiology of Tuberculosis (ICEPT-3, 5th–6th July 2022, Institute of Biology, University of Szeged, Szeged, Hungary)
Edited by György Pálfi, Olivier Dutour, Tamás Hajdu, Christophe Sola, Albert Zink

DOI

DOI: 10.1016/j.tube.2023.102428

Journal article2023

Re-examination of the Subalyuk Neanderthal remains uncovers signs of probable TB infection (Subalyuk Cave, Hungary)

Pálfi G, Molnár E, Bereczki Z, Coqueugniot H, Dutour O, Tillier A, Rosendahl W, Sklánitz A,

Frank Maixner, Albert Zink

In 1932, skeletal remains of two Neanderthal individuals, a young adult female and a 3–4–year-old child, were discovered in Subalyuk Cave in Northern Hungary [1,2]. Results of the anthropological examination were published some years after this important discovery. Methodological progress encouraged re-examination of the material during the last few years. Radiocarbon dating revealed a chronological age of 39,732–39,076 cal. BP for the adult female and 36,117–35,387 cal. BP for the child [3]. Morphological paleopathological studies of these Neanderthal remains uncovered distinct evidence of skeletal infections. Alterations of the adult individual's sacrum suggest probable early-stage sacroiliitis, while several vertebral bodies indicate superficial osseous remodelling of infectious origin. Traces of pathological lesions were observed on the endocranial surface of the child's skull, reflecting a reaction of meningeal tissues, a consequence of a probable TB-related meningeal infectious process. Results of recent paleomicrobiological examinations – lipid biomarker and aDNA studies – support the morphological diagnosis of probable TB infections [4].

DOI

DOI: 10.1016/j.tube.2023.102419

All Publications

Histology of pulmonary tuberculosis in a 19th-century mummy from Comiso (Sicily, Italy)
Gaeta R, Giuffra V, Maixner F, Aringhieri G, Fornaciari A (2024)
Zeitschriftenartikel
International Journal of Paleopathology

https://doi.org/10.1016/j.ijpp.2024.11.001

Multidisciplinary study on the role of bone lesions in the paleopathological diagnosis of tuberculosis in ancient human remains
Zink A, Kanik J, Lerchl J, Mari B, Lee J, Harbeck M, Maixner F (2024)
Vortrag

Conference: European Meeting of the Paleopathology Association PPA | Leiden | 21.8.2024 - 24.8.2024

Hit or miss: A metagenomic evaluation of intra-bone variability of host pathogen load in tuberculosis-infected human remains
Jäger HY, Atz Zanotelli D, Maixner F, Nicklisch N, Alt KW, Meller H, Pap I, Szikossy I, Pàlfi G, Zink A (2023)
Zeitschriftenartikel
Tuberculosis

https://doi.org/10.1016/j.tube.2023.102392

Our partners

Department of Biological Anthropology, University of Szeged, Dugonics Ter, Szeged, Hungary

Hungarian Natural History Museum

Project Team

Frank Maixner

Albert Zink

Technische
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Journal article2024

Histology of pulmonary tuberculosis in a 19th-century mummy from Comiso (Sicily, Italy)

Gaeta R, Giuffra V, Maixner F, Aringhieri G, Fornaciari A

Frank Maixner

Objective: The aim of this study is to investigate potential evidence of tuberculosis in mummified remains.

Materials: The natural mummy of an anonymous friar from the mortuary chapel of the church of Santa Maria della Grazia in Comiso (Sicily)

Conclusions: These findings are compatible with a chronic infectious-inflammatory disease, likely a calcification of a previous Ghon complex of an apical nodular tuberculosis.

Significance: Our study supports the great spread of the disease in the 19th century; a time when it reached its maximum peak in Europe.

Limitations: Molecular investigations failed to detect traces of Mycobacterium tuberculosis DNA in the sample.

DOI

DOI: 10.1016/j.ijpp.2024.11.001

EvolTB