The capacity of microbial pathogens to alter their host tropism leading to epidemics in distinct host species populations is a global public and veterinary health concern. To investigate the molecular basis of a bacterial host-switching event in a tractable host species, we traced the evolutionary trajectory of the common rabbit clone of Staphylococcus aureus. We report that it evolved through a likely human-to-rabbit host jump over 40 years ago and that only a single naturally occurring nucleotide mutation was required and sufficient to convert a human-specific S. aureus strain into one that could infect rabbits. Related mutations were identified at the same locus in other rabbit strains of distinct clonal origin, consistent with convergent evolution. This first report of a single mutation that was sufficient to alter the host tropism of a microorganism during its evolution highlights the capacity of some pathogens to readily expand into new host species populations.

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We thank J. Etienne for helpful advice, O. Schneewind, M. Woolhouse and Í. Lasa for comments on the manuscript, C. Cervera and E. Blas for their support with the in vivo experiments, and R. Cartwright for excellent technical assistance. We are grateful to Edinburgh Genomics (Roslin Institute) for sequencing services. This work was supported by grants BIO2011-30503-C02-01, Eranet-pathogenomics PIM2010EPA-00606 and Consolider-Ingenio CSD2009-00006 from Ministerio de Ciencia e Innovación (Spain) and strategic grant funding from the University of Glasgow to J.R.P.; by a project grant (BB/I013873/1) and institute strategic grant funding from the Biotechnology and Biological Sciences Research Council (UK) to J.R.F., in addition to a doctoral training grant from the Medical Research Council (UK) to J.R.F.; and by grants AGL2011-30170-CO2-02 (Ministerio de Ciencia e Innovación, Spain) and GV2013-077 (Conselleria d'Educació, Cultura i Esport, Generalitat Valenciana) to D.V.

Author information

Author notes

    • David Viana
    • , María Comos
    •  & Paul R McAdam

    These authors contributed equally to this work.

    • J Ross Fitzgerald
    •  & José R Penadés

    These authors jointly supervised this work.


  1. Biomedical Research Institute, Universidad CEU Cardenal Herrera, Valencia, Spain.

    • David Viana
    •  & Laura Selva
  2. Centro de Investigación y Tecnología Animal, Instituto Valenciano de Investigaciones Agrarias (CITA-IVIA), Segorbe, Spain.

    • María Comos
  3. The Roslin Institute, University of Edinburgh, Easter Bush Campus, Edinburgh, UK.

    • Paul R McAdam
    • , Caitriona M Guinane
    •  & J Ross Fitzgerald
  4. Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.

    • Melissa J Ward
  5. Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK.

    • Beatriz M González-Muñoz
    •  & Simon J Foster
  6. Centre National de Référence des Staphylocoques, Université Lyon, Lyon, France.

    • Anne Tristan
  7. Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC), Valencia, Spain.

    • José R Penadés
  8. Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

    • José R Penadés


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J.R.F. and J.R.P. conceived and designed the study. D.V., M.C. and L.S. generated and characterized the different mutant strains. P.R.M., M.J.W. and C.M.G. performed the genomic studies. B.M.G.-M. and S.J.F. measured D-Ala content. A.T. provided human strains. J.R.P., J.R.F. and S.J.F. supervised the research. J.R.F. and J.R.P. wrote the manuscript and obtained funding.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to J Ross Fitzgerald or José R Penadés.

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