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Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):3639-44. doi: 10.1073/pnas.1525637113. Epub 2016 Mar 8.

Human symbionts inject and neutralize antibacterial toxins to persist in the gut.

Author information

1
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;
2
Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195;
3
Department of Integrative Biology, University of Texas, Austin, TX 78712;
4
Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
5
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201;
6
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.
7
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.

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.

KEYWORDS:

gut microbiome; microbial ecology; symbiosis; type VI secretion

PMID:
26957597
PMCID:
PMC4822603
DOI:
10.1073/pnas.1525637113
[Indexed for MEDLINE]
Free PMC Article

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