Laurie Comstock

Research Summary
The human intestinal microbiota is a complex and dynamic consortium of microbes that is crucial for human health and disease prevention. Our lab has been studying the abundant bacterial members of this ecosystem to understand how they interact with each other both cooperatively and antagonistically to form these health-promoting communities. We use basic microbiological, genetic, biochemical, and gnotobiotic mouse analyses, combined with genomic, metagenomic and computational analyses to understand these complex interactions. We have discovered numerous classes of new antimicrobial proteins that these bacteria use to compete in their ecosystem, and we are studying their mechanisms of action, ecological properties, and how we may translate these molecules for human health benefits. Another focus of the lab is the evolution of microbes in the human gut and how genetic elements horizontally transferred between bacterial species personalize each individual’s gut microbiota and the phenotypes and community benefits conferred by these shared genetic elements.
Keywords
Gut symbionts, Microbiota, Microbiome, Bacteroidales, Bacterial interactions, Bacterial antagonism, Antimicrobial proteins
Education
  • Brigham and Women's Hospital / Harvard Medical School, Boston, MA, Postdoctoral Fellowship Bacteroides fragilis genetics 1996
  • University of Maryland Medical Center / Center for Vaccine Development , Baltimore, MD, Postdoctoral Fellowship Vibrio cholerae pathogenesis 1995
  • Wake Forest University Medical Center / Bowman Gray School of Medicine, Winston-Salem, NC, PhD Microbiology and Immunology 1991
  • Rensselaer Polytechnic Institute, Troy, NY, BS Biology 1987
Biosciences Graduate Program Association
Publications
  1. Evans JC, McEneany VL, Coyne MJ, Caldwell EP, Sheahan ML, Von SS, Coyne EM, Tweten RK, Comstock LE. A proteolytically activated antimicrobial toxin encoded on a mobile plasmid of Bacteroidales induces a protective response. Nat Commun. 2022 Jul 23; 13(1):4258. View in: PubMed

  2. Bao H, Coyne MJ, García-Bayona L, Comstock LE. Analysis of Effector and Immunity Proteins of the GA2 Type VI Secretion Systems of Gut Bacteroidales. J Bacteriol. 2022 07 19; 204(7):e0012222. View in: PubMed

  3. Tomek MB, Janesch B, Braun ML, Taschner M, Figl R, Grünwald-Gruber C, Coyne MJ, Blaukopf M, Altmann F, Kosma P, Kählig H, Comstock LE, Schäffer C. A Combination of Structural, Genetic, Phenotypic and Enzymatic Analyses Reveals the Importance of a Predicted Fucosyltransferase to Protein O-Glycosylation in the Bacteroidetes. Biomolecules. 2021 11 30; 11(12). View in: PubMed

  4. Matano LM, Coyne MJ, García-Bayona L, Comstock LE. Bacteroidetocins Target the Essential Outer Membrane Protein BamA of Bacteroidales Symbionts and Pathogens. mBio. 2021 10 26; 12(5):e0228521. View in: PubMed

  5. García-Bayona L, Coyne MJ, Comstock LE. Mobile Type VI secretion system loci of the gut Bacteroidales display extensive intra-ecosystem transfer, multi-species spread and geographical clustering. PLoS Genet. 2021 04; 17(4):e1009541. View in: PubMed

  6. Smith WPJ, Brodmann M, Unterweger D, Davit Y, Comstock LE, Basler M, Foster KR. The evolution of tit-for-tat in bacteria via the type VI secretion system. Nat Commun. 2020 10 26; 11(1):5395. View in: PubMed

  7. 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. Analysis of a phase-variable restriction modification system of the human gut symbiont Bacteroides fragilis. Nucleic Acids Res. 2020 11 04; 48(19):11040-11053. View in: PubMed

  8. García-Bayona L, Coyne MJ, Hantman N, Montero-Llopis P, Von SS, Ito T, Malamy MH, Basler M, Barquera B, Comstock LE. Nanaerobic growth enables direct visualization of dynamic cellular processes in human gut symbionts. Proc Natl Acad Sci U S A. 2020 09 29; 117(39):24484-24493. View in: PubMed

  9. Smith WPJ, Vettiger A, Winter J, Ryser T, Comstock LE, Basler M, Foster KR. The evolution of the type VI secretion system as a disintegration weapon. PLoS Biol. 2020 05; 18(5):e3000720. View in: PubMed

  10. Ito T, Gallegos R, Matano LM, Butler NL, Hantman N, Kaili M, Coyne MJ, Comstock LE, Malamy MH, Barquera B. Genetic and Biochemical Analysis of Anaerobic Respiration in Bacteroides fragilis and Its Importance In Vivo. mBio. 2020 02 04; 11(1). View in: PubMed

  11. García-Bayona L, Comstock LE. Utilizing Ribose Compounds: How Bacteroides PUL It Off. Cell Host Microbe. 2020 01 08; 27(1):6-8. View in: PubMed

  12. García-Bayona L, Comstock LE. Streamlined Genetic Manipulation of Diverse Bacteroides and Parabacteroides Isolates from the Human Gut Microbiota. mBio. 2019 08 13; 10(4). View in: PubMed

  13. 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 08 01; 10(1):3460. View in: PubMed

  14. Coyne MJ, Comstock LE. Type VI Secretion Systems and the Gut Microbiota. Microbiol Spectr. 2019 03; 7(2). View in: PubMed

  15. 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 04 15; 201(8). View in: PubMed

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

  17. 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. View in: PubMed

  18. 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. View in: PubMed

  19. 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). View in: PubMed

  20. 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). View in: PubMed

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

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

  23. Coyne MJ, Comstock LE. A New Pillar in Pilus Assembly. Cell. 2016 Apr 21; 165(3):520-1. View in: PubMed

  24. Chatzidaki-Livanis M, Geva-Zatorsky N, Comstock LE. Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species. Proc Natl Acad Sci U S A. 2016 Mar 29; 113(13):3627-32. View in: PubMed

  25. Coyne MJ, Roelofs KG, Comstock LE. Type VI secretion systems of human gut Bacteroidales segregate into three genetic architectures, two of which are contained on mobile genetic elements. BMC Genomics. 2016 Jan 15; 17:58. View in: PubMed

  26. Liu S, da Cunha AP, Rezende RM, Cialic R, Wei Z, Bry L, Comstock LE, Gandhi R, Weiner HL. The Host Shapes the Gut Microbiota via Fecal MicroRNA. Cell Host Microbe. 2016 Jan 13; 19(1):32-43. View in: PubMed

  27. Chatzidaki-Livanis M, Comstock LE. Friend turned foe: a role for bacterial sulfatases in colitis. Cell Host Microbe. 2015 May 13; 17(5):540-1. View in: PubMed

  28. Chatzidaki-Livanis M, Coyne MJ, Comstock LE. An antimicrobial protein of the gut symbiont Bacteroides fragilis with a MACPF domain of host immune proteins. Mol Microbiol. 2014 Dec; 94(6):1361-74. View in: PubMed

  29. Rakoff-Nahoum S, Comstock LE. Immunology: Starve a fever, feed the microbiota. Nature. 2014 Oct 30; 514(7524):576-7. View in: PubMed

  30. Coyne MJ, Zitomersky NL, McGuire AM, Earl AM, Comstock LE. Evidence of extensive DNA transfer between bacteroidales species within the human gut. mBio. 2014 Jun 17; 5(3):e01305-14. View in: PubMed

  31. Rakoff-Nahoum S, Coyne MJ, Comstock LE. An ecological network of polysaccharide utilization among human intestinal symbionts. Curr Biol. 2014 Jan 06; 24(1):40-49. View in: PubMed

  32. Wieland Brown LC, Penaranda C, Kashyap PC, Williams BB, Clardy J, Kronenberg M, Sonnenburg JL, Comstock LE, Bluestone JA, Fischbach MA. Production of a-galactosylceramide by a prominent member of the human gut microbiota. PLoS Biol. 2013 Jul; 11(7):e1001610. View in: PubMed

  33. Zitomersky NL, Atkinson BJ, Franklin SW, Mitchell PD, Snapper SB, Comstock LE, Bousvaros A. Characterization of adherent bacteroidales from intestinal biopsies of children and young adults with inflammatory bowel disease. PLoS One. 2013; 8(6):e63686. View in: PubMed

  34. Coyne MJ, Fletcher CM, Chatzidaki-Livanis M, Posch G, Schaffer C, Comstock LE. Phylum-wide general protein O-glycosylation system of the Bacteroidetes. Mol Microbiol. 2013 May; 88(4):772-83. View in: PubMed

  35. Posch G, Pabst M, Neumann L, Coyne MJ, Altmann F, Messner P, Comstock LE, Schäffer C. "Cross-glycosylation" of proteins in Bacteroidales species. Glycobiology. 2013 May; 23(5):568-77. View in: PubMed

  36. Coyne MJ, Fletcher CM, Reinap B, Comstock LE. UDP-glucuronic acid decarboxylases of Bacteroides fragilis and their prevalence in bacteria. J Bacteriol. 2011 Oct; 193(19):5252-9. View in: PubMed

  37. Zitomersky NL, Coyne MJ, Comstock LE. Longitudinal analysis of the prevalence, maintenance, and IgA response to species of the order Bacteroidales in the human gut. Infect Immun. 2011 May; 79(5):2012-20. View in: PubMed

  38. Fletcher CM, Coyne MJ, Comstock LE. Theoretical and experimental characterization of the scope of protein O-glycosylation in Bacteroides fragilis. J Biol Chem. 2011 Feb 04; 286(5):3219-26. View in: PubMed

  39. Troy EB, Carey VJ, Kasper DL, Comstock LE. Orientations of the Bacteroides fragilis capsular polysaccharide biosynthesis locus promoters during symbiosis and infection. J Bacteriol. 2010 Nov; 192(21):5832-6. View in: PubMed

  40. Chatzidaki-Livanis M, Weinacht KG, Comstock LE. Trans locus inhibitors limit concomitant polysaccharide synthesis in the human gut symbiont Bacteroides fragilis. Proc Natl Acad Sci U S A. 2010 Jun 29; 107(26):11976-80. View in: PubMed

  41. Chatzidaki-Livanis M, Coyne MJ, Comstock LE. A family of transcriptional antitermination factors necessary for synthesis of the capsular polysaccharides of Bacteroides fragilis. J Bacteriol. 2009 Dec; 191(23):7288-95. View in: PubMed

  42. Comstock LE. Importance of glycans to the host-bacteroides mutualism in the mammalian intestine. Cell Host Microbe. 2009 Jun 18; 5(6):522-6. View in: PubMed

  43. Fletcher CM, Coyne MJ, Villa OF, Chatzidaki-Livanis M, Comstock LE. A general O-glycosylation system important to the physiology of a major human intestinal symbiont. Cell. 2009 Apr 17; 137(2):321-31. View in: PubMed

  44. Coyne MJ, Chatzidaki-Livanis M, Paoletti LC, Comstock LE. Role of glycan synthesis in colonization of the mammalian gut by the bacterial symbiont Bacteroides fragilis. Proc Natl Acad Sci U S A. 2008 Sep 02; 105(35):13099-104. View in: PubMed

  45. Belzer C, Comstock LE. Expression of phase variable surface molecules of Bacteroides species from healthy and clinical stool. J Pediatr Gastroenterol Nutr. 2008 Apr; 46 Suppl 1:E15-6. View in: PubMed

  46. Chatzidaki-Livanis M, Coyne MJ, Roche-Hakansson H, Comstock LE. Expression of a uniquely regulated extracellular polysaccharide confers a large-capsule phenotype to Bacteroides fragilis. J Bacteriol. 2008 Feb; 190(3):1020-6. View in: PubMed

  47. Coyne MJ, Comstock LE. Niche-specific features of the intestinal bacteroidales. J Bacteriol. 2008 Jan; 190(2):736-42. View in: PubMed

  48. Comstock LE. Microbiology: the inside story. Nature. 2007 Aug 02; 448(7153):542-4. View in: PubMed

  49. Sebastian S, Dillon ST, Lynch JG, Blalock LT, Balon E, Lee KT, Comstock LE, Conlan JW, Rubin EJ, Tzianabos AO, Kasper DL. A defined O-antigen polysaccharide mutant of Francisella tularensis live vaccine strain has attenuated virulence while retaining its protective capacity. Infect Immun. 2007 May; 75(5):2591-602. View in: PubMed

  50. Fletcher CM, Coyne MJ, Bentley DL, Villa OF, Comstock LE. Phase-variable expression of a family of glycoproteins imparts a dynamic surface to a symbiont in its human intestinal ecosystem. Proc Natl Acad Sci U S A. 2007 Feb 13; 104(7):2413-8. View in: PubMed

  51. Roche-Hakansson H, Chatzidaki-Livanis M, Coyne MJ, Comstock LE. Bacteroides fragilis synthesizes a DNA invertase affecting both a local and a distant region. J Bacteriol. 2007 Mar; 189(5):2119-24. View in: PubMed

  52. Comstock LE, Kasper DL. Bacterial glycans: key mediators of diverse host immune responses. Cell. 2006 Sep 08; 126(5):847-50. View in: PubMed

  53. Coyne MJ, Reinap B, Lee MM, Comstock LE. Human symbionts use a host-like pathway for surface fucosylation. Science. 2005 Mar 18; 307(5716):1778-81. View in: PubMed

  54. Weinacht KG, Roche H, Krinos CM, Coyne MJ, Parkhill J, Comstock LE. Tyrosine site-specific recombinases mediate DNA inversions affecting the expression of outer surface proteins of Bacteroides fragilis. Mol Microbiol. 2004 Sep; 53(5):1319-30. View in: PubMed

  55. Comstock LE, Coyne MJ. Bacteroides thetaiotaomicron: a dynamic, niche-adapted human symbiont. Bioessays. 2003 Oct; 25(10):926-9. View in: PubMed

  56. Coyne MJ, Weinacht KG, Krinos CM, Comstock LE. Mpi recombinase globally modulates the surface architecture of a human commensal bacterium. Proc Natl Acad Sci U S A. 2003 Sep 02; 100(18):10446-51. View in: PubMed

  57. Krinos CM, Coyne MJ, Weinacht KG, Tzianabos AO, Kasper DL, Comstock LE. Extensive surface diversity of a commensal microorganism by multiple DNA inversions. Nature. 2001 Nov 29; 414(6863):555-8. View in: PubMed

  58. Coyne MJ, Tzianabos AO, Mallory BC, Carey VJ, Kasper DL, Comstock LE. Polysaccharide biosynthesis locus required for virulence of Bacteroides fragilis. Infect Immun. 2001 Jul; 69(7):4342-50. View in: PubMed

  59. Kalka-Moll WM, Wang Y, Comstock LE, Gonzalez SE, Tzianabos AO, Kasper DL. Immunochemical and biological characterization of three capsular polysaccharides from a single Bacteroides fragilis strain. Infect Immun. 2001 Apr; 69(4):2339-44. View in: PubMed

  60. Comstock LE, Pantosti A, Kasper DL. Genetic diversity of the capsular polysaccharide C biosynthesis region of Bacteroides fragilis. Infect Immun. 2000 Nov; 68(11):6182-8. View in: PubMed

  61. Coyne MJ, Kalka-Moll W, Tzianabos AO, Kasper DL, Comstock LE. Bacteroides fragilis NCTC9343 produces at least three distinct capsular polysaccharides: cloning, characterization, and reassignment of polysaccharide B and C biosynthesis loci. Infect Immun. 2000 Nov; 68(11):6176-81. View in: PubMed

  62. Comstock LE, Coyne MJ, Tzianabos AO, Kasper DL. Interstrain variation of the polysaccharide B biosynthesis locus of Bacteroides fragilis: characterization of the region from strain 638R. J Bacteriol. 1999 Oct; 181(19):6192-6. View in: PubMed

  63. Comstock LE, Coyne MJ, Tzianabos AO, Pantosti A, Onderdonk AB, Kasper DL. Analysis of a capsular polysaccharide biosynthesis locus of Bacteroides fragilis. Infect Immun. 1999 Jul; 67(7):3525-32. View in: PubMed

  64. Losonsky GA, Lim Y, Motamedi P, Comstock LE, Johnson JA, Morris JG, Tacket CO, Kaper JB, Levine MM. Vibriocidal antibody responses in North American volunteers exposed to wild-type or vaccine Vibrio cholerae O139: specificity and relevance to immunity. Clin Diagn Lab Immunol. 1997 May; 4(3):264-9. View in: PubMed

  65. Comstock LE, Johnson JA, Michalski JM, Morris JG, Kaper JB. Cloning and sequence of a region encoding a surface polysaccharide of Vibrio cholerae O139 and characterization of the insertion site in the chromosome of Vibrio cholerae O1. Mol Microbiol. 1996 Feb; 19(4):815-26. View in: PubMed

  66. Faruque SM, Comstock L, Kaper JB, Albert MJ. Distribution of Zonula occludens toxin (zot) gene among clinical isolates of Vibrio cholerae O1 from Bangladesh and Africa. J Diarrhoeal Dis Res. 1994 Sep; 12(3):222-4. View in: PubMed

  67. Comstock LE, Fikrig E, Shoberg RJ, Flavell RA, Thomas DD. A monoclonal antibody to OspA inhibits association of Borrelia burgdorferi with human endothelial cells. Infect Immun. 1993 Feb; 61(2):423-31. View in: PubMed

  68. Tacket CO, Losonsky G, Nataro JP, Comstock L, Michalski J, Edelman R, Kaper JB, Levine MM. Initial clinical studies of CVD 112 Vibrio cholerae O139 live oral vaccine: safety and efficacy against experimental challenge. J Infect Dis. 1995 Sep; 172(3):883-6. View in: PubMed

  69. Fasano A, Fiorentini C, Donelli G, Uzzau S, Kaper JB, Margaretten K, Ding X, Guandalini S, Comstock L, Goldblum SE. Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J Clin Invest. 1995 Aug; 96(2):710-20. View in: PubMed

  70. Comstock LE, Maneval D, Panigrahi P, Joseph A, Levine MM, Kaper JB, Morris JG, Johnson JA. The capsule and O antigen in Vibrio cholerae O139 Bengal are associated with a genetic region not present in Vibrio cholerae O1. Infect Immun. 1995 Jan; 63(1):317-23. View in: PubMed

  71. Thomas DD, Comstock LE. Interaction of Lyme disease spirochetes with cultured eucaryotic cells. Infect Immun. 1989 Apr; 57(4):1324-6. View in: PubMed

  72. Comstock LE, Thomas DD. Penetration of endothelial cell monolayers by Borrelia burgdorferi. Infect Immun. 1989 May; 57(5):1626-8. View in: PubMed

  73. Comstock LE, Thomas DD. Characterization of Borrelia burgdorferi invasion of cultured endothelial cells. Microb Pathog. 1991 Feb; 10(2):137-48. View in: PubMed