The human intestinal microbiota is composed of hundreds of microbial species and strains and is one of the densest microbial ecosystems on Earth. Despite the heightened interest in the intestinal microbiota, investigations into the dynamic microbial interactions that occur within this ecosystem are still in their infancy. Little is known about how bacterial species become established in the mammalian intestine, the interactions that occur between strains and species, and the factors that influence microbial stability and diversity in the ecosystem.
Our lab studies the biology of a predominant order of bacteria of the human intestine, the Bacteroidales. These are the most abundant Gram-negative bacteria of this ecosystem and establish mutualistic relationships with their hosts in that they both receive and provide beneficial properties. We study properties and molecules of these bacteria that allow them to survive and thrive in the human gut. We are also very interested in population and community dynamics of the intestinal microbiota, community stability, and how these bacteria interact with other members of the intestinal microbiota. A main focus of the lab is the study of competitive or antagonistic interactions among gut Bacteroidales species mediated by the production of molecules that directly harm other members.
We have identified antimicrobial toxins or toxin delivery systems in more than half of human gut Bacteroidales strains and we have shown that many of these genes are encoded on conjugative elements that are readily transferred to other co-resident Bacteroidales members in the human intestine. As the Bacteroidales toxins we have identified are new types of antibacterial molecules, we are elucidating their mechanisms of intoxication of target cells as well as their role in shaping gut microbial communities.
By understanding the bacterial factors that contribute to compositional changes in this ecosystem, we will eventually be able to use these data to manipulate the microbial community in select individuals to improve health outcomes. We are also studying other translational aspects of these antibacterial molecules including their use to combat bacterial pathogens.
- García-Bayona L, Coyne MJ, Comstock LE. 2021. Mobile Type VI secretion system loci of the gut Bacteroidales display extensive intraecosystem transfer, multi-species spread and geographical clustering. PLoS Genetics 17(4):e1009541.
- Ben-Assa N, Coyne MJ, Fomenkov A, Livny J, Robins WP, Muniesa M, Carey V, Carasso S, Gefen T, Jofre J, Roberts RJ, Comstock LE, Geva-Zatorsky N. 2020. Analysis of a phase-variable restriction modification system of the human gut symbiont Bacteroides fragilis. Nucleic Acids Research 48(19):11040–11053.
- García-Bayona L, Coyne MJ, Hantman N, Montero-Llopis P, Von SS, Ito T, Malamy MH, Basler M, Barquera B, Comstock LE. 2020. Nanaerobic growth enables direct visualization of dynamic cellular processes in human gut symbionts. Proceedings of the National Academy of Sciences USA 117(39):24484-24493.
- Smith WPJ, Vettiger A, Winter J, Ryser T, Comstock LE, Basler M, Foster KR. 2020. The evolution of the type VI secretion system as a disintegration weapon. Plos Biology 18(5):e3000720.
- Ito T, Gallegos R, Matano LM, Butler NL, Hantman N, Kaili M, Coyne MJ, Comstock LE, Malamy MH, Barquera B. 2020. Genetic and biochemical analysis of anaerobic respiration in Bacteroides fragilis and its importance in vivo. mBio 11(1):e03238-19.
- García-Bayona L, Comstock LE. 2019. Streamlined genetic manipulation of diverse Bacteroides and Parabacteroides isolates from the human gut microbiota. mBio 10(4):e01762-19.
- Coyne MJ, Béchon N, Matano LM, McEneany VL, Chatzidaki-Livanis M, Comstock LE. 2019. A family of anti-Bacteroidales peptide toxins wide-spread in the human gut microbiota. Nature Communications 10(1):3460.
- Coyne MJ, Comstock LE. 2019. Type VI secretion systems and the gut microbiota. Microbiol Spectrum 7(2):PSIB-0009-2018.
- Shumaker AM, Laclare McEneany V, Coyne MJ, Silver PA, Comstock LE. 2019. Identification of a fifth antibacterial toxin produced by a single Bacteroides fragilis strain. J Bacteriol. 201(8):e00577-18.
- García-Bayona L, Comstock LE. 2018. Bacterial antagonism in host-associated microbial communities. Science 361(6408):aat2456.
- McEneany VL, Coyne MJ, Chatzidaki-Livanis M, Comstock LE. 2018. Acquisition of MACPF domain-encoding genes is the main contributor to LPS glycan diversity in gut Bacteroides species. ISME J doi:10.1038/s41396-018-0244-4
- Chatzidaki-Livanis M, Coyne MJ, Roelofs KG, Gentyala RR, Caldwell JM, Comstock LE. 2017. Gut symbiont Bacteroides fragilis secretes a eukaryotic-like ubiquitin protein that mediates intraspecies antagonism. mBio 8:e01902-01917.
- Roelofs KG, Coyne MJ, Gentyala RR, Chatzidaki-Livanis M, Comstock LE. 2016. Bacteroidales secreted antimicrobial proteins target surface molecules necessary for gut colonization and mediate competition in vivo. mBio 7:e01055-01016.
- Rakoff-Nahoum S, Foster KR, Comstock LE. 2016. The evolution of cooperation within the gut microbiota. Nature 533:255-259.
- Coyne MJ, Comstock LE. 2016. A new pillar in pilus assembly. Cell 165:520-521.
- Chatzidaki-Livanis M, Geva-Zatorsky N, Comstock LE. 2016. Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species. Proc Natl Acad Sci USA 113:3627-3632.
- Coyne MJ, Roelofs KG, Comstock LE. 2016. Type VI secretion systems of human gut Bacteroidales segregate into three genetic architectures, two of which are contained on mobile genetic elements. BMC Genomics 17:58.
- Comstock LE. 2016. Small RNAs repress expression of polysaccharide utilization loci of gut Bacteroides species. J Bacteriol 198:2396-2398.
- Liu S, da Cunha AP, Rezende RM, Cialic R, Wei Z, Bry L, Comstock LE, Gandhi R, Weiner HL. 2016. The host shapes the gut microbiota via fecal microRNA. Cell Host Microbe 19:32-43.
- Rakoff-Nahoum S, Coyne MJ, Comstock LE. 2014. An ecological network of polysaccharide utilization among human intestinal symbionts. Curr Biol 24:40-49.
- Coyne MJ, Zitomersky NL, McGuire AM, Earl AM, Comstock LE. 2014. Evidence of extensive DNA transfer between Bacteroidales species within the human gut. mBio 5:e01305-01314-e01305-01314.
- Chatzidaki-Livanis M, Coyne MJ, Comstock LE. 2014. An antimicrobial protein of the gut symbiont Bacteroides fragilis with a MACPF domain of host immune proteins. Mol Microbiol 94:1361-1374.
© 2019 The Comstock Laboratory, Brigham & Women's Hospital, Department of Medicine, Division of Infectious Diseases, 181 Longwood Avenue, Boston, MA 02115 USA