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Laurie Elizabeth Comstock, PhD
Associate Microbiologist, Brigham and Women's Hospital
Professor of Medicine, Harvard Medical School

Brigham and Women's Hospital
Department of Medicine
Infectious Diseases
75 Francis Street
Boston, MA 02115


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Research Narrative:

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.


Education:
Bowman Gray School of Medicine, Wake forest University, 1991, PhD

Additional News:



Publications (Pulled from Harvard Catalyst Profiles):

1. Coyne MJ, Béchon N, Matano LM, McEneany VL, Chatzidaki-Livanis M, Comstock LE. A family of anti-Bacteroidales peptide toxins wide-spread in the human gut microbiota. Nat Commun. 2019 Aug 01; 10(1):3460.

2. Shumaker AM, Laclare McEneany V, Coyne MJ, Silver PA, Comstock LE. Identification of a Fifth Antibacterial Toxin Produced by a Single Bacteroides fragilis Strain. J Bacteriol. 2019 Apr 15; 201(8).

3. Coyne MJ, Comstock LE. Type VI Secretion Systems and the Gut Microbiota. Microbiol Spectr. 2019 03; 7(2).

4. García-Bayona L, Comstock LE. Bacterial antagonism in host-associated microbial communities. Science. 2018 09 21; 361(6408).

5. McEneany VL, Coyne MJ, Chatzidaki-Livanis M, Comstock LE. Acquisition of MACPF domain-encoding genes is the main contributor to LPS glycan diversity in gut Bacteroides species. ISME J. 2018 12; 12(12):2919-2928.

6. Lee-Sarwar K, Kelly RS, Lasky-Su J, Moody DB, Mola AR, Cheng TY, Comstock LE, Zeiger RS, O'Connor GT, Sandel MT, Bacharier LB, Beigelman A, Laranjo N, Gold DR, Bunyavanich S, Savage JH, Weiss ST, Brennan PJ, Litonjua AA. Intestinal microbial-derived sphingolipids are inversely associated with childhood food allergy. J Allergy Clin Immunol. 2018 07; 142(1):335-338.e9.

7. Chatzidaki-Livanis M, Coyne MJ, Roelofs KG, Gentyala RR, Caldwell JM, Comstock LE. Gut Symbiont Bacteroides fragilis Secretes a Eukaryotic-Like Ubiquitin Protein That Mediates Intraspecies Antagonism. MBio. 2017 11 28; 8(6).

8. Comstock LE. Small RNAs Repress Expression of Polysaccharide Utilization Loci of Gut Bacteroides Species. J Bacteriol. 2016 09 15; 198(18):2396-8.

9. Roelofs KG, Coyne MJ, Gentyala RR, Chatzidaki-Livanis M, Comstock LE. Bacteroidales Secreted Antimicrobial Proteins Target Surface Molecules Necessary for Gut Colonization and Mediate Competition In Vivo. MBio. 2016 08 23; 7(4).

10. Rakoff-Nahoum S, Foster KR, Comstock LE. The evolution of cooperation within the gut microbiota. Nature. 2016 05 12; 533(7602):255-9.