title: Transferred interbacterial antagonism genes augment eukaryotic innate immune function.
abstract: Horizontal gene transfer allows organisms to rapidly acquire adaptive traits. 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-option. 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 system. 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.
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
authors.forename: Seemay
authors.initials: S
authors.lastname: Chou
authors.affiliation: 1] Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA [2] Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Daugherty
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
authors.forename: S Brook
authors.initials: SB
authors.lastname: Peterson
authors.affiliation: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, UK.
authors.forename: Jacob
authors.initials: J
authors.lastname: Biboy
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Youyun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1] Microbial Sciences Institute, Yale University, New Haven, Connecticut 06516, USA [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06516, USA.
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Jutras
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.
authors.forename: Lillian K
authors.initials: LK
authors.lastname: Fritz-Laylin
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Ferrin
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Harding
authors.affiliation: 1] Microbial Sciences Institute, Yale University, New Haven, Connecticut 06516, USA [2] Howard Hughes Medical Institute, Yale University, New Haven, Connecticut 06516, USA [3] Department of Microbial Pathogenesis, Yale University, New Haven, Connecticut 06516, USA [4] Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06516, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Jacobs-Wagner
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: X Frank
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, UK.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Vollmer
authors.affiliation: 1] Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA [2] Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Harmit S
authors.initials: HS
authors.lastname: Malik
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Mougous
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001419:Bacteria / Q000166:cytology / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology; D058947:Bacterial Secretion Systems; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000166:cytology / Q000254:growth & development / Q000276:immunology; D002473:Cell Wall / Q000378:metabolism; D017124:Conserved Sequence / Q000235:genetics; D056890:Eukaryota / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D022761:Gene Transfer, Horizontal / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics*; D007113:Immunity, Innate / Q000235:genetics; D018884:Ixodes / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010802:Phylogeny; D013379:Substrate Specificity
chemical_list: D058947:Bacterial Secretion Systems; D001427:Bacterial Toxins; D000581:Amidohydrolases; C019665:amidase