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

Aaron G. Wexler, Yiqiao Bao, John C. Whitney, Louis Marie Bobay, Joao B. Xavier, Whitman B. Schofield, Natasha A. Barry, Alistair B. Russell, Bao Q. Tran, Young Ah Goo, David R. Goodlett, Howard Ochman, Joseph D. Mougous, Andrew L. Goodman, Ralph R. Isberg

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


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 micro-bial 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 multi-phylum 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.

Original languageEnglish
Pages (from-to)3639-3644
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - Mar 29 2016


  • Gut microbiome
  • Microbial ecology
  • Symbiosis
  • Type VI secretion


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