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Antibiotic resistance is ancient


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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Figure 1: Stratigraphic profile and location of Bear Creek site.
Figure 2: Genetic diversity of ancient antibiotic resistance elements.
Figure 3: Ancient vancomycin resistance elements.

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


  1. Livermore, D. M. Has the era of untreatable infections arrived? J. Antimicrob. Chemother. 64, i29–i36 (2009)

    Article  CAS  Google Scholar 

  2. Wright, G. D. The antibiotic resistome: the nexus of chemical and genetic diversity. Nature Rev. Microbiol. 5, 175–186 (2007)

    Article  CAS  Google Scholar 

  3. Hughes, V. M. & Datta, N. Conjugative plasmids in bacteria of the ‘pre-antibiotic’ era. Nature 302, 725–726 (1983)

    Article  ADS  CAS  Google Scholar 

  4. D’Costa, V. M., McGrann, K. M., Hughes, D. W. & Wright, G. D. Sampling the antibiotic resistome. Science 311, 374–377 (2006)

    Article  ADS  Google Scholar 

  5. Dantas, G., Sommer, M. O. A., Oluwasegun, R. D. & Church, G. M. Bacteria subsisting on antibiotics. Science 320, 100–103 (2008)

    Article  ADS  CAS  Google Scholar 

  6. Sommer, M. O. A., Dantas, G. & Church, G. M. Functional characterization of the antibiotic resistance reservoir in the human microflora. Science 325, 1128–1131 (2009)

    Article  ADS  CAS  Google Scholar 

  7. Baltz, R. H. Antibiotic discovery from actinomycetes: will a renaissance follow the decline and fall? SIM News 55, 186–196 (2005)

    Google Scholar 

  8. Hall, B. G. & Barlow, M. Evolution of the serine β-lactamases: past, present and future. Drug Resist. Updat. 7, 111–123 (2004)

    Article  CAS  Google Scholar 

  9. Mindlin, S. Z., Soina, V. S., Petrova, M. A. & Gorlenko, Z. M. Isolation of antibiotic resistance bacterial strains from Eastern Siberia permafrost sediments. Russ. J. Genet. 44, 27–34 (2008)

    Article  CAS  Google Scholar 

  10. Froese, D. G., Zazula, G. D. & Reyes, A. V. Seasonality of the late Pleistocene Dawson tephra and exceptional preservation of a buried riparian surface in central Yukon Territory, Canada. Quat. Sci. Rev. 25, 1542–1551 (2006)

    Article  ADS  Google Scholar 

  11. Froese, D. G. et al. The Klondike goldfields and Pleistocene environments of Beringia. GSA Today 19, 4–10 (2009)

    Article  Google Scholar 

  12. Brock, F., Froese, D. G. & Roberts, R. G. Low temperature (LT) combustion of sediments does not necessarily provide accurate radiocarbon ages for site chronology. Quat. Geochronol. 5, 625–630 (2010)

    Article  Google Scholar 

  13. Willerslev, E., Hansen, A. J. & Poinar, H. N. Isolation of nucleic acids and cultures from fossil ice and permafrost. Trends Ecol. Evol. 19, 141–147 (2004)

    Article  Google Scholar 

  14. Harington, C. R. & Clulow, F. V. Pleistocene mammals from Gold Run Creek, Yukon Territory. Can. J. Earth Sci. 10, 697–759 (1973)

    Article  ADS  Google Scholar 

  15. Zazula, G. D. et al. Ice-age steppe vegetation in east Beringia. Nature 423, 603 (2003)

    Article  ADS  CAS  Google Scholar 

  16. Haile, J. et al. Ancient DNA reveals late survival of mammoth and horse in interior Alaska. Proc. Natl Acad. Sci. USA 106, 22352–22357 (2009)

    Article  ADS  CAS  Google Scholar 

  17. Gilichinsky, D. et al. in Psychrophiles: From Biodiversity to Biotechnology (eds Margesin, R., Schinner, F., Marx, J.-C. & Gerday, C. ) 83–102 (Springer, 2008)

    Book  Google Scholar 

  18. Doyle, D., McDowall, K. J., Butler, M. J. & Hunter, I. S. Characterization of an oxytetracycline-resistance gene, otrA, of Streptomyces rimosus. Mol. Microbiol. 5, 2923–2933 (1991)

    Article  CAS  Google Scholar 

  19. Courvalin, P. Vancomycin resistance in gram-positive cocci. Clin. Infect. Dis. 42, S25–S34 (2006)

    Article  CAS  Google Scholar 

  20. Pearson, W. R. & Lipman, D. J. Improved tools for biological sequence comparison. Proc. Natl Acad. Sci. USA 85, 2444–2448 (1988)

    Article  ADS  CAS  Google Scholar 

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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.

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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.

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

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The authors declare no competing financial interests.

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The file contains Supplementary Text, Supplementary Figures 1-14 with legends and Supplementary Tables 1-12. (PDF 3142 kb)

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D’Costa, V., King, C., Kalan, L. et al. Antibiotic resistance is ancient. Nature 477, 457–461 (2011).

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