Abstract

The discovery of antibiotics more than 70 years ago initiated a period of drug innovation and implementation in human and animal health and agriculture. These discoveries were tempered in all cases by the emergence of resistant microbes1,2. This history has been interpreted to mean that antibiotic resistance in pathogenic bacteria is a modern phenomenon; this view is reinforced by the fact that collections of microbes that predate the antibiotic era are highly susceptible to antibiotics3. Here we report targeted metagenomic analyses of rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost sediments and the identification of a highly diverse collection of genes encoding resistance to β-lactam, tetracycline and glycopeptide antibiotics. Structure and function studies on the complete vancomycin resistance element VanA confirmed its similarity to modern variants. These results show conclusively that antibiotic resistance is a natural phenomenon that predates the modern selective pressure of clinical antibiotic use.

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Accessions

Primary accessions

GenBank/EMBL/DDBJ

Data deposits

The metagenomic sequences determined from permafrost are deposited in GenBank under accession numbers JN316287–JN366376.

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Acknowledgements

We thank A. Guarné for assistance in X-ray data collection. This work was supported by Canada Research Chairs to D.F., H.N.P. and G.D.W., a Canadian Institutes of Health Research operating grant to G.D.W. (MOP-79488) and a scholarship to V.M.D., and by grants from the Natural Sciences and Engineering Research Council of Canada to D.F. and H.N.P. and scholarship to C.E.K.

Author information

Author notes

    • Vanessa M. D’Costa
    •  & Christine E. King

    These authors contributed equally to this work.

Affiliations

  1. Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5

    • Vanessa M. D’Costa
    • , Lindsay Kalan
    • , Mariya Morar
    • , Hendrik N. Poinar
    •  & Gerard D. Wright
  2. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5

    • Vanessa M. D’Costa
    • , Lindsay Kalan
    • , Mariya Morar
    •  & Gerard D. Wright
  3. McMaster Ancient DNA Centre, Department of Anthropology, McMaster University, Hamilton, Ontario, Canada, L8S 4L9

    • Christine E. King
    • , Carsten Schwarz
    •  & Hendrik N. Poinar
  4. Department of Biology, McMaster University, Hamilton, Ontario, Canada, L8S 4K1

    • Christine E. King
    • , Wilson W. L. Sung
    • , G. Brian Golding
    •  & Hendrik N. Poinar
  5. Department of Earth and Atmospheric Sciences, University of Alberta, Edmonton, Alberta, Canada, T6G 2E3

    • Duane Froese
    •  & Fabrice Calmels
  6. Yukon Palaeontology Program, Department of Tourism and Culture, Yukon Government, PO Box 2703, Whitehorse, Yukon, Canada, Y1A 2C6

    • Grant Zazula
  7. Muséum National d’Histoire Naturelle, UMR 7206 Eco-anthropologie, 57 rue Cuvier, CP139, 75231 Paris cedex 05, France

    • Regis Debruyne

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Contributions

D.F., G.Z. and F.C. collected permafrost cores and performed geochemical analyses followed by subsampling by C.S., V.M.D. and C.E.K. C.E.K performed ancient DNA laboratory work and 454 sequencing. V.M.D. designed primers for resistance genes, 16S and gfp. V.M.D. and C.E.K. designed and optimized the qPCR assays, and cloned and sequenced the resistance gene products. R.D. independently confirmed the results in France. L.K. purified and characterized VanA, and M.M. crystallized VanA and determined the three-dimensional structure. W.S., G.B.G., C.E.K. and H.N.P. processed and analysed the floral/faunal data; V.M.D. and G.B.G. performed phylogenetic and bioinformatic analyses of the resistance gene sequences. H.N.P. and G.D.W. conceived the project, and V.M.D., C.E.K., D.F., H.N.P. and G.D.W. wrote the manuscript. All authors edited the final draft.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Hendrik N. Poinar or Gerard D. Wright.

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    Supplementary Information

    The file contains Supplementary Text, Supplementary Figures 1-14 with legends and Supplementary Tables 1-12.

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DOI

https://doi.org/10.1038/nature10388

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