ANCIENT PATHOGENS

Molecular analysis of the microbiome and of infectious diseases in ancient human remains - from capture-sequencing to metagenomics diagnostics.

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  • Project duration: December 2012 - December 2022
  • Project status: ongoing
  • Funding:
    Internal funding EURAC (Project)
  • Total project budget: €530,000.00

Ancient skeletal and soft tissue samples can still contain traces of the original bacterial DNA. This applies both to the DNA of human commensals (e.g. intestinal bacteria) and to the genetic material of pathogens. Thereby, genome wide analysis of ancient pathogens provides information on the onset and spread of chronic infectious diseases such as tuberculosis or leprosy and helps to identify the causative agents of major human epidemics such as the plague. Furthermore, the metagenomic study of ancient human microbiomes provide novel insights into the composition and possible changes of human microbial communities over the last millennia. The biomolecular investigation of pathogens in ancient human remains represents an emerging field of research which provides considerable insight into the history and evolution of infectious diseases. The applied diagnostic approaches in paleomicobiology range from the histological detection to the PCR-based characterization of ancient pathogens. More recently, the era of high-throughput sequencing paved new ways to analyze ancient DNA resulting e.g. in the first complete genome of the causative agent of Black Death, Yersinia pestis. However there are obstacles yet to overcome such as the limitations of PCR-based approaches in analyzing highly degraded ancient DNA extracts or the development of bioinformatics pipelines to screen complex metagenomic datasets for ancient pathogens.

The aim of this project will be to improve the DNA-based detection of the microbiome incl. pathogens in ancient human remains. To further optimize molecular diagnostics approaches the EURAC Institute for Mummy Studies has access to an variety of tissue samples with possible tuberculosis, brucellosis and malaria infection. Moreover, together with our cooperation partner from Vienna and Stockholm we are analyzing the metagenomic data of the Iceman´s genomic survey in order to establish a bioinformatics pipeline for the de novo detection of commensals and pathogens in metagenomic datasets of ancient human remains. Thereby obtained knowledge is currently also applied to shotgun datasets of Tuberculosis positive skeletal material. In addition we seek for molecular traces of other diseases such as e.g. leprosy, syphilis, malaria and plague in ancient human remains.

Publications
Linear polyacrylamide is highly efficient in precipitating and purifying environmental and ancient DNA
Maixner F, Mitterer C, Jäger HY, Sarhan MS, Valverde G, Lücker S, Piombino-Mascali D, Szikossy I, Molnár E, Pálfi G, Pap I, Cipollini G, Zink A (2021)
Journal article
Methods in Ecology and Evolution

https://doi.org/10.1111/2041-210X.13772

Verification of tuberculosis infection among Vác mummies (18th century CE, Hungary) based on lipid biomarker profiling with a new HPLC-HESI-MS approach
Váradi OA, Rakk D, Spekker O, Terhes G, Urbán E, Berthon W, Pap I, Szikossy I, Maixner F, Zink A, Vágvólgyi C, Donoghue H, Minnikin D, Szekeres A, Pálfi G (2021)
Journal article
Tuberculosis

More information: https://doi.org/10.1016/j.tube.2020.102037

https://doi.org/10.1016/j.tube.2020.102037

https://hdl.handle.net/10863/16368

Reconstruction of ancient microbial genomes from the human gut
Wibowo MC, Yang Z, Borry M, Hübner A, Huang KD, Tierney BT, Zimmerman S, Barajas-Olmos F, Contreras-Cubas C, García-Ortiz H, Martínez-Hernández A, Luber JM, Kirstahler P, Blohm T, Smiley FE, Arnold R, Ballal SA, Pamp SJ, Russ J, Maixner F, Rota-Stabelli O, Segata N, Reinhard K, Orozco L, Warinner C, Snow M, LeBlanc S, Kostic AD (2021)
Journal article
Nature

More information: https://www.nature.com/articles/s41586-021-03532-0

https://doi.org/10.1038/s41586-021-03532-0

https://hdl.handle.net/10863/17191

Ancient DNA analysis of rare genetic bone disorders
Maixner F, Gresky J, Zink A (2021)
Journal article
International Journal of Paleopathology

More information: https://doi.org/10.1016/j.ijpp.2021.04.009

https://doi.org/10.1016/j.ijpp.2021.04.009

https://hdl.handle.net/10863/17193

Molecular and microscopic analysis of human paleofeces from the salt mines in Hallstatt, Austria, provide precious insights into dietary habits and gut microbiome composition of Iron Age miners
Maixner F, Sarhan MS, Huang KD, Tett A, Schoenafinger A, Zingale S, Blanco-Míguez A, Manghi P, Cemper-Kiesslich J, Rosendahl W, Kusebauch U, Morrone SR, Hoopmann MR, Rota-Stabelli O, Rattei T, Moritz RL, Oeggl K, Segata N, Zink A, Reschreiter H, Kowarik K (2021)
Presentation/Speech

Conference: ISBA9| 9TH INTERNATIONAL SYMPOSIUM ON BIOMOLECULAR ARCHAEOLOGY | Toulouse : 1.6.2021 - 4.6.2021

https://hdl.handle.net/10863/18542

Recovery of ancient human- and microbial DNA from cave bones and-sediments
Sarhan M, Lehmkuhl A, Wieland G, Franken M, Zink A, Maixner F (2021)
Presentation/Speech

Conference: Bioinformatics Virtual Coordination Network Virtual Conference| Holistic Bioinformatic Approaches used in Microbiome Research | : 7.6.2021 - 11.6.2021

https://hdl.handle.net/10863/18947

Ancient DNA diffuses from human bones to cave stones
Sarhan MS, Lehmkuhl A, Straub R, Tett A, Wieland G, Francken M, Zink A, Maixner F (2021)
Journal article
iScience

https://doi.org/10.1016/j.isci.2021.103397

https://hdl.handle.net/10863/20140

Analysis of 1,321 Eubacterium rectale genomes from metagenomes uncovers complex phylogeographic population structures and subspecies functional adaptations
Karcher N, Pasolli E, Asnicar F, Huang K, Tett A, Manara S, Armanini F, Bain D, Duncan SH, Louis P, Zolfo M, Manghi P, Raffaetà R, Rota-Stabelli O, Collado MC, Zeller G, Falush D, Maixner F, Walker AW, Huttenhower C, Segata N (2020)
Journal article
Genome Biology

https://doi.org/10.1186/s13059-020-02042-y

https://hdl.handle.net/10863/14778

Lipid biomarker based verification of TB infection in mother’s and daughter’s mummified human remains (Vác Mummy Collection, 18th century, CE, Hungary)
Váradia OA, Szikossy I, Spekkera O, Rakk D, Terhes G, Urbán E, Berthon W, Pap I, Maixner F, Zink A, Vágvölgyi C, Donoghue HD, Minnikin DE, Pálfi´G, Szekeres A (2020)
Journal article
Acta Biologica Szegediensis

More information: http://abs.bibl.u-szeged.hu/index.php/abs

https://doi.org/10.14232/abs.2020.2.99-109

https://hdl.handle.net/10863/16814

The Prevotella copri complex comprises four distinct clades that are underrepresented in Westernized populations
Tett A, Huang KD, Asnicar F, Fehlner-Peach H, Pasolli E, Karcher N, Armanini F, Manghi P, Bonham K, Zolfo M, De Filippis F, Magnabosco C, Bonneau R, Lusingu R, Amuasi J, Reinhard K, Rattei T, Boulund F, Engstrand L, Zink A, Collado MC, Littman DR, Eibach D, Ercolini D, Rota-Stabelli O, Huttenhower C, Maixner F, Segata N (2019)
Journal article
Cell Host & Microbe

https://doi.org/10.1016/j.chom.2019.08.018

https://hdl.handle.net/10863/11462

Molecular Reconstruction of the Diet in Human Stool Samples
Maixner F (2019)
Journal article
mSystems

https://doi.org/10.1128/mSystems.00634-19

https://hdl.handle.net/10863/12257

Helicobacter pylori in ancient human remains
Maixner F, Thorell K, Granehäll L, Linz B, Moodley Y, Rattei T, Engstrand L, Zink A (2019)
Journal article
World Journal of Gastroenterology

More information: https://www.wjgnet.com/1007-9327/full/v25/i42/6289.htm

https://doi.org/10.3748/wjg.v25.i42.6289

https://hdl.handle.net/10863/12256

The Iceman's Last Meal Consisted of Fat, Wild Meat, and Cereals
Maixner F, Turaev D, Cazenave-Gassiot A, Janko M, Krause-Kyora B, Hoopmann MR, Kusebauch U, Sartain M, Guerriero G, O'Sullivan N, Teasdale M, Cipollini G, Paladin A, Mattiangeli V, Samadelli M, Putzer A, Tecchiati U, Meissen J, Palazoglu M, Rausch P, Lösch S, Kim BJ, Baines JF, Gostner P, An HJ, Malfertheiner P, Egarter-Vigl E, Stark RW, Keller A, Bishop D, Wenk M, Engstrand L, Moritz RL, Bradley DG, Fiehn O, Nebel A, Oeggl K, Doble P, Franke A, Rattei T, Grimm R, Zink A (2018)
Journal article
Current Biology

https://doi.org/10.1016/j.cub.2018.05.067

https://hdl.handle.net/10863/6829

The comparative study of two extraction methods for ancient DNA: silica suspension method and ultracentrifugal concentrator method
Lee EJ, Maixner F, Zink A (2018)
Journal article
Analytical Science & Technology

https://doi.org/10.5806/AST.2018.31.2.65

https://hdl.handle.net/10863/6824

miRNAs in ancient tissue specimens of the Tyrolean Iceman
Keller A, Kreis S, Leidinger P, Maixner F, Ludwig N, Backes C, Galata V, Guerriero G, Fehlmann T, Franke A, Meder B, Zink A, Meese E (2017)
Journal article
Molecular Biology and Evolution

https://doi.org/10.1093/molbev/msw291

https://hdl.handle.net/10863/7334

Tuberculosis in early medieval Switzerland: osteological and molecular evidence from Courroux
Cooper C, Fellner R, Heubi O, Maixner F, Zink A, Lösch S (2016)
Journal article
Swiss Medical Weekly

https://doi.org/10.4414/smw.2016.14269

https://hdl.handle.net/10863/6670

The 5300-year-old Helicobacter pylori genome of the Iceman
Maixner F, Krause-Kyora B, Turaev D, Herbig A, Hoopmann MR, Hallows JL, Kusebauch U, Vigl EE, Malfertheiner P, Megraud F, O'Sullivan N, Cipollini G, Coia V, Samadelli M, Engstrand L, Linz B, Moritz RL, Grimm R, Krause J, Nebel A, Moodley Y, Rattei T, Zink A (2016)
Journal article
Science

https://doi.org/10.1126/science.aad2545

https://hdl.handle.net/10863/6124

Our partners

University College Dublin, School of Archeology

Reiss-Engelhorn-Museen Mannheim

Max Planck Institute for the Science of Human History

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

Medizinische Universität Wien, Forensische Medizin, Fachbereich Forensische Anthropologie

Centre for Translational Microbiome Research (CTMR), Karolinska Institute, Stockholm, Sweden

University of Vienna, CUBE - Division of Computational Systems Biology, Department of Microbiology ...

Universita degli Studi di Firenze, Facultà di Medicina e Chirurgia

Project Team
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MummyLabs

Development and centralization of the laboratory infrastructures of the Institute for Mummy Studies ...

Duration: December 2017 - June 2022Funding: FESR (EU funding / Project)

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