title: Human symbionts inject and neutralize antibacterial toxins to persist in the gut.
abstract: The human gut microbiome is a dynamic and densely populated microbial community that can provide important benefits to its host. Cooperation and competition for nutrients among its constituents only partially explain community composition and interpersonal variation. Notably, certain human-associated Bacteroidetes--one of two major phyla in the gut--also encode machinery for contact-dependent interbacterial antagonism, but its impact within gut microbial communities remains unknown. Here we report that prominent human gut symbionts persist in the gut through continuous attack on their immediate neighbors. Our analysis of just one of the hundreds of species in these communities reveals 12 candidate antibacterial effector loci that can exist in 32 combinations. Through the use of secretome studies, in vitro bacterial interaction assays and multiple mouse models, we uncover strain-specific effector/immunity repertoires that can predict interbacterial interactions in vitro and in vivo, and find that some of these strains avoid contact-dependent killing by accumulating immunity genes to effectors that they do not encode. Effector transmission rates in live animals can exceed 1 billion events per minute per gram of colonic contents, and multiphylum communities of human gut commensals can partially protect sensitive strains from these attacks. Together, these results suggest that gut microbes can determine their interactions through direct contact. An understanding of the strategies human gut symbionts have evolved to target other members of this community may provide new approaches for microbiome manipulation.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510; Microbial Sciences Institute, Yale University School of Medicine, West Haven, CT 06516;
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Wexler
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510; Microbial Sciences Institute, Yale University School of Medicine, West Haven, CT 06516;
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195;
authors.forename: John C
authors.initials: JC
authors.lastname: Whitney
authors.affiliation: Department of Integrative Biology, University of Texas, Austin, TX 78712;
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Bobay
authors.affiliation: Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
authors.forename: Joao B
authors.initials: JB
authors.lastname: Xavier
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510; Microbial Sciences Institute, Yale University School of Medicine, West Haven, CT 06516;
authors.forename: Whitman B
authors.initials: WB
authors.lastname: Schofield
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510; Microbial Sciences Institute, Yale University School of Medicine, West Haven, CT 06516;
authors.forename: Natasha A
authors.initials: NA
authors.lastname: Barry
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195;
authors.forename: Alistair B
authors.initials: AB
authors.lastname: Russell
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201;
authors.forename: Bao Q
authors.initials: BQ
authors.lastname: Tran
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201;
authors.forename: Young Ah
authors.initials: YA
authors.lastname: Goo
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201;
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.affiliation: Department of Integrative Biology, University of Texas, Austin, TX 78712;
authors.forename: Howard
authors.initials: H
authors.lastname: Ochman
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195; Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA 98195.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Mougous
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510; Microbial Sciences Institute, Yale University School of Medicine, West Haven, CT 06516; andrew.goodman@yale.edu.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Goodman
mesh_terms: D000818:Animals; D001441:Bacteroides fragilis / Q000235:genetics / Q000276:immunology / Q000502:physiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016680:Genome, Bacterial; D005856:Germ-Free Life; D006801:Humans; D008297:Male; D051379:Mice; D023421:Models, Animal; D010802:Phylogeny; D013559:Symbiosis / Q000235:genetics / Q000276:immunology / Q000502:physiology; D000069376:Type VI Secretion Systems / Q000235:genetics / Q000276:immunology / Q000502:physiology
chemical_list: D000069376:Type VI Secretion Systems
keywords: gut microbiome; microbial ecology; symbiosis; type VI secretion