title: Eighteenth-century genomes show that mixed infections were common at time of peak tuberculosis in Europe.
abstract: Tuberculosis (TB) was once a major killer in Europe, but it is unclear how the strains and patterns of infection at 'peak TB' relate to what we see today. Here we describe 14 genome sequences of M. tuberculosis, representing 12 distinct genotypes, obtained from human remains from eighteenth-century Hungary using metagenomics. All our historic genotypes belong to M. tuberculosis Lineage 4. Bayesian phylogenetic dating, based on samples with well-documented dates, places the most recent common ancestor of this lineage in the late Roman period. We find that most bodies yielded more than one M. tuberculosis genotype and we document an intimate epidemiological link between infections in two long-dead individuals. Our results suggest that metagenomic approaches usefully inform detection and characterization of historical and contemporary infections.
authors.affiliation: Microbiology and Infection Unit, Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Gemma L
authors.initials: GL
authors.lastname: Kay
authors.affiliation: Microbiology and Infection Unit, Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Sergeant
authors.affiliation: Microbiology and Infection Unit, Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Zhemin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Microbiology and Infection Unit, Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Jacqueline Z-M
authors.initials: JZ
authors.lastname: Chan
authors.affiliation: Microbiology and Infection Unit, Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Millard
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Joshua
authors.initials: J
authors.lastname: Quick
authors.affiliation: Department of Anthropology, Hungarian Natural History Museum, Ludovika tér 2-6, 1083 Budapest, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Szikossy
authors.affiliation: Department of Anthropology, Hungarian Natural History Museum, Ludovika tér 2-6, 1083 Budapest, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Pap
authors.affiliation: 1] Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 9112102, Israel [2] Centre for Clinical Microbiology, Division of Infection and Immunity, University College London, London NW3 2PF, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Spigelman
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Loman
authors.affiliation: Microbiology and Infection Unit, Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Achtman
authors.affiliation: Centre for Clinical Microbiology, Division of Infection and Immunity, University College London, London NW3 2PF, UK.
authors.forename: Helen D
authors.initials: HD
authors.lastname: Donoghue
authors.affiliation: Microbiology and Infection Unit, Division of Translational and Systems Medicine, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Pallen
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D060085:Coinfection / Q000382:microbiology*; D004269:DNA, Bacterial / Q000032:analysis*; D005060:Europe / Q000453:epidemiology; D005260:Female; D016680:Genome, Bacterial / Q000235:genetics*; D005838:Genotype; D049671:History, 18th Century; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D008297:Male; D056186:Metagenomics; D008875:Middle Aged; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D010802:Phylogeny; D014376:Tuberculosis / Q000453:epidemiology / Q000266:history / Q000382:microbiology*; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial
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