Horizontal gene transfer allows organisms to rapidly acquire adaptive traits1. Although documented instances of horizontal gene transfer from bacteria to eukaryotes remain rare, bacteria represent a rich source of new functions potentially available for co-option2. One benefit that genes of bacterial origin could provide to eukaryotes is the capacity to produce antibacterials, which have evolved in prokaryotes as the result of eons of interbacterial competition. The type VI secretion amidase effector (Tae) proteins are potent bacteriocidal enzymes that degrade the cell wall when delivered into competing bacterial cells by the type VI secretion system3. Here we show that tae genes have been transferred to eukaryotes on at least six occasions, and that the resulting domesticated amidase effector (dae) genes have been preserved for hundreds of millions of years through purifying selection. We show that the dae genes acquired eukaryotic secretion signals, are expressed within recipient organisms, and encode active antibacterial toxins that possess substrate specificity matching extant Tae proteins of the same lineage. Finally, we show that a dae gene in the deer tick Ixodes scapularis limits proliferation of Borrelia burgdorferi, the aetiologic agent of Lyme disease. Our work demonstrates that a family of horizontally acquired toxins honed to mediate interbacterial antagonism confers previously undescribed antibacterial capacity to eukaryotes. We speculate that the selective pressure imposed by competition between bacteria has produced a reservoir of genes encoding diverse antimicrobial functions that are tailored for co-option by eukaryotic innate immune systems.

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We thank L. Holland for assistance with transcriptome analysis, D. Vollmer and C. Aldridge for PG preparation, J. Parrish for microinjection assistance, J. Young for assistance with phylogenetic analyses, H. Merrikh for sharing equipment, and T. Alber, C. Fuqua, K. Clay, E. Rynkiewicz, U. Pal, C. Grundner, G. Nester, P. Singh and members of the Malik and Mougous laboratories for helpful discussions. This work was funded by the National Institutes of Health (AI080609 to J.D.M. and AI083640 to X.F.Y.), the Defense Threat Reduction Agency (HDTRA-1-13-014 to J.D.M.) and the BBSRC (BB/I020012/1 to W.V.). S.C. was supported by a Howard Hughes Medical Institute (HHMI)-sponsored Life Sciences Research Foundation fellowship, M.A.F. by the American Society for Microbiology Undergraduate Research Fellowship, and M.D.D. by an Irvington Institute Fellowship from the Cancer Research Institute. C.J.-W. and H.S.M. are investigators of the HHMI. J.D.M. holds an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund.

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Author notes

    • Seemay Chou
    •  & Matthew D. Daugherty

    These authors contributed equally to this work.


  1. Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA

    • Seemay Chou
    • , S. Brook Peterson
    • , Michael A. Ferrin
    • , Brittany N. Harding
    •  & Joseph D. Mougous
  2. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA

    • Matthew D. Daugherty
    •  & Harmit S. Malik
  3. Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA

    • Matthew D. Daugherty
    •  & Harmit S. Malik
  4. Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, UK

    • Jacob Biboy
    •  & Waldemar Vollmer
  5. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA

    • Youyun Yang
    •  & X. Frank Yang
  6. Microbial Sciences Institute, Yale University, New Haven, Connecticut 06516, USA

    • Brandon L. Jutras
    •  & Christine Jacobs-Wagner
  7. Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06516, USA

    • Brandon L. Jutras
    •  & Christine Jacobs-Wagner
  8. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA

    • Lillian K. Fritz-Laylin
  9. Department of Microbial Pathogenesis, Yale University, New Haven, Connecticut 06516, USA

    • Christine Jacobs-Wagner
  10. Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06516, USA

    • Christine Jacobs-Wagner


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S.C., M.D.D., H.S.M. and J.D.M. designed the study. S.C., M.D.D., S.B.P., J.B., Y.Y., B.L.J., L.K.F.-L., M.A.F., B.N.H., C.J.-W., X.F.Y., W.V., H.S.M. and J.D.M. performed experiments, analysed data and provided intellectual input into aspects of this study. S.C., M.D.D., S.B.P., H.S.M. and J.D.M. wrote the manuscript; all authors contributed to its editing.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Joseph D. Mougous.

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