Laurie E. Comstock, PhD Associate Professor of Medicine
Harvard Medical School
Associate Microbiologist, Department
The long term goals of the laboratory are to elucidate mechanisms used by members of the intestinal microbiota to establish and maintain symbiotic relationships in the mammalian intestine. We study the Bacteroides species, which are the most abundant Gram-negative bacteria of this ecosystem, in some people accounting for 20% of the total intestinal bacteria.
One active area of study in the lab is analysis of the synthesis, regulation, and significance of the enormous number of glycosylated molecules made by these bacteria. A single strain of Bacteroides fragilis synthesizes eight distinct surface capsular polysaccharides that are expressed in a phase variable manner dictated by inversion of DNA segments containing the promoters of the polysaccharide biosynthesis operons.
Our continuing studies include elucidation of the complex regulatory network that governs capsular polysaccharide expression as well as determining the benefit that phase variation of surface molecules provides these bacteria for their survival in the mammalian intestine. The Bacteroides spp. also synthesize glycoproteins that we are just beginning to analyze to understand their functional contributions to the ability of these bacteria to colonize and thrive in the mammalian intestine.
Our laboratory is also investigating other molecular mechanisms unique to these bacteria that contribute to their predominance in the complex and competitive human intestinal ecosystem. We are studying defensive strategies these bacteria may employ to protect themselves from harmful products produced by the host and other intestinal members, as well as offensive mechanisms they may use to thwart competitors.
Fletcher, C. M., M. J. Coyne, O. F. Villa, M. Chatzidaki-Livanis, and L. E. Comstock. 2009. A general O-glycosylation system important to the physiology of a major human intestinal symbiont. Cell 137:321-331. [abstract]
Coyne, M. J., M. Chatzidaki-Livanis, L . C. Paoletti, and L. E. Comstock. 2008. Role of glycan synthesis in colonization of the mammalian gut by the bacterial symbiont Bacteroides fragilis. Proc Natl Acad Sci USA 105:13099-13104. [abstract]
Chatzidaki-Livanis, M., M. J. Coyne, H. Roche-Hakansson, and L. E. Comstock. 2008. Expression of a uniquely regulated extracellular polysaccharide confers a large-capsule phenotype to Bacteroides fragilis. J Bacteriol 190:1020-1026. [abstract]
Coyne, M. J., and L. E. Comstock. 2008. Niche-specific features of the intestinal Bacteroidales. J Bacteriol 190:736-742. [abstract]
Fletcher, C. M., M. J. Coyne, D. L. Bentley, O. F. Villa, and L. E. Comstock. 2007. Phase-variable expression of a family of glycoproteins imparts a dynamic surface to a symbiont in its human intestinal ecosystem. Proc Natl Acad Sci USA 104:2413-2418. [abstract]
Roche-Hakansson, H., M. Chatzidaki-Livanis, M. J. Coyne, and L. E. Comstock. 2007. Bacteroides fragilis synthesizes a DNA invertase affecting both a local and a distant region. J Bacteriol 189:2119-2124. [abstract]
Coyne, M. J., Reinap B., Lee M. M., and Comstock L. E. 2005. Human symbionts use a host-like pathway for surface fucosylation. Science 307:1778-1781. [abstract]page last updated April 17, 2009