Areas of Interest
Complex carbohydrate utilization by human gut bacteria
My lab seeks to understand how human gut bacteria recognize and import the carbohydrates that transit their environment. The glycan (ie carbohydrate) landscape of the gut is constantly changing through the variety of foods that we eat. In addition, mucus and cells are shed from the intestines that contain complex sugar structures that also act as food for these bacteria. The types and abundance of carbohydrates in this environment shape the composition of the gut community meaning that we can change the bacterial community in our intestinal tract by changing what we eat. The composition of this community (ie the types and abundance of certain species) dictates its metabolic output, which influences the progression and outcome of various diseases such as diabetes, obesity, colorectal cancer and inflammatory bowel diseases. In addition, these bacteria supply us with short chain fatty acids that positively influence our health.
My work is centered on the structure and function of bacterial cell surface proteins involved in the capture, degradating and import of carbohydrates from the environment. A primary technique we use to understand how proteins interact with carbohydrates is protein crystallography, which allows us to visualize the protein-carbohydrate interface, and isothermal titration calorimetry, which we use to measure the affinity and specificity of the protein-carbohydrate interaction. We can then make predictions about how these proteins drive glycan update, and test these hypotheses in vivo by disrupting or mutating the genes encoding these proteins to determine how bacterial growth is affected. We also utilize single molecule fluorescence imaging (a collaborative effort with Dr. Julie Biteen in Chemistry) to track the movement of proteins during glycan uptake in order to visualize this metabolic process in real time. This interdisciplinary approach has allowed us to better understand the process of glycan uptake in key human gut symbionts including Bacteroides thetaiotaomicron, Bacteroides ovatus, Eubacterium rectale and Ruminococcus bromii.
Wefers D, Cavalcante JJV, Schendel RR, Deveryshetty J, Wang K, Wawrzak Z, Mackie R, Koropatkin N, Cann I. 2017. Biochemical assignment of two cryptic proteins in Bacteroides intestinalis as bifunctional esterases and their synergistic activities with cognate xylan degrading enzymes. J Mol Biol. 429(16):2509-2527.
Cockburn DW, Koropatkin NM. 2016. Polysaccharide degradation by the intestinal microbiota and its influence on human health and disease. J Mol Biol .428(16):3230-5.
Foley MH, Cockburn DW, Koropatkin NM. 2016. The Sus operon: a model system for starch uptake by the human gut Bacteroidetes. Cell Mol Life Sci : 73(14):2603-17.
Tauzin AS, Kwiatkowski KJ, Orlovsky NI, Smith CJ, Creagh AL, Haynes CA, Wawrzak Z, Brumer H, Koropatkin NM. 2016. Molecular dissection of xyloglucan recognition in a prominent human gut symbiont. mBio 7(2): e02134-15.
Larsbrink J, Zhu Y, Kharade SS, Kwiatkowski KJ, Eijsink VG, Koropatkin NM , McBride MJ, Pope PB. 2016. A polysaccharide utilization locus from Flavobacterium johnsoniae enables conversion of recalcitrant chitin. Biotechnol Biofuels . 9:260.
Cockburn, D.W., Orlovsky, N.I., Foley, M.H., Kwiatkowski, K.J., Bahr, C.M., Maynard, M., Demeler, B., and N.M. Koropatkin. 2014. Molecular details of a starch utilization pathway in the human gut symbiont Eubacterium rectale. Mol Microbiol. Jan;95(2):209-30.
Ze X, Ben David Y, Laverde-Gomez JA, Dassa B, Sheridan PO, Duncan SH, Louis P, Henrissat B, Juge N, Koropatkin NM, Bayer EA, Flint HJ. 2015. Unique Organization of Extracellular Amylases into Amylosomes in the Resistant Starch-Utilizing Human Colonic Firmicutes Bacterium Ruminococcus bromii. MBio. Sep 29; 6(5). pii: e01058-15. doi: 10.1128/mBio.01058-15.
Cameron, E.A., Kwiatkowski, K.J., Lee, B.H., Hamaker, B.R., Koropatkin, N.M., and E.C. Martens. 2014. Multifunctional nutrient-binding proteins adapt human symbiotic bacteria for glycan competition in the gut by separately promoting enhanced sensing and catalysis.MBio. Sep 9;5(5):e01441-14.
Karunatilaka, K.S., Cameron, E.A., Martens, E.C., Koropatkin, N.M., and J.S. Biteen. 2014. Superresolution imaging captures carbohydrate utilization dynamics in human gut symbionts. MBio. Nov 11;5(6):e02172. doi: 10.1128/mBio.02172-14.
Larsbrink, J., Rogers, T.E., Hemsworth, G.R., McKee, L.S., Tauzin, A.S., Spadiut, O., Klinter, S., Pudlo, N.A., Urs, K., Koropatkin, N.M., Creagh, A.L., Haynes, C.A., Kelly, A.G., Cederholm, S.N., Davies, G.J., Martens, E.C., and H. Brumer. 2014. A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes. Nature. 506(7489): 498-502.
Koropatkin, N.M., Cameron, E.A. and E.C. Martens. 2012. How glycan metabolism shapes the human gut microbiota. Nat. Rev. Microbiol. 10(5): 323-35.
Bolam, D.N. and N.M. Koropatkin. 2012. Glycan recognition and sensing by the Bacteroidetes Sus-like systems. Curr. Opin. Struc. Biol. 22(5): 563-9. Koropatkin, N.M., Martens, E.C., Gordon, J.I., and T.J. Smith. 2008. Starch catabolism by a prominent human gut symbiont is directed by the recognition of amylose helices. Structure. 16 (7): 1105-15.