Ph.D. Microbiology, The Ohio State University (2000)
Research Interests
The role of microbial metabolism of quaternary amines in cardiovascular disease:
Cardiovascular disease is the leading cause of death worldwide. In recent years, studies have shown a clear link between consumption of foods rich in quaternary amine compounds such as choline and carnitine and the development of atherosclerosis. This association is due to the action of gut microbiota that can cleave quaternary amines in a way that yields a product called trimethylamine (TMA). TMA then travels through the blood to the liver where it becomes oxidized to a compound called trimethylamine N-oxide (TMAO). TMAO then acts as a direct precursor to the development of atherosclerosis, or deposition of plaques along the inside of blood vessels. The conversion of quaternary amines to TMA is strictly dependent on gut microbiota and yet not all gut microbiota contribute to heart disease in this manner. Our research has shown that some gut microbiota, including those that are plentiful in the gut, possess the ability to demethylate quaternary amines rather than cleave them, and thus do not generate TMA. Therefore, many gut microbes appear to catabolize quaternary amines in ways that would lessen the risk of atherosclerosis rather than heighten that risk. We recently isolated a gut bacterium capable of degrading quaternary amines without producing TMA and have initially characterized its metabolism. We are currently interested in learning more about this form of microbial metabolism.
Quaternary amine dependent methanogenesis:
We are also interested in the metabolism of methylotrophic methanogens. Methanogens generate methane (natural gas) as the end product of their metabolism. Methane is both an important fuel source and potent greenhouse gas. We hypothesized that some strains of methylotrophic methanogens are able to use quaternary amines as substrates and this led us to the successful isolation of two novel strains of methanogens capable of quaternary amine dependent methanogenesis. We are currently investigating the metabolism of these organisms and elucidating the pathways by which they convert quaternary amines to methane. We have identified the pathway for glycine betaine dependent methanogenesis, which uses a nonpyrrolysine homolog of the TMA methyltransferase. More recently we have identified the first methyltransferase for both tetramethylammonium and choline, a nonpyrrrolysine homolog of the monomethylamine methyltransferase. We are currently further elucidating these pathways and identifying the pathways used in the complete demethylation of choline to ethanolamine. Our work has ecological, evolutionary, and human health significance.
Selected Publications
Kashyap JS, Das D, Ticak T, Creighbaum AJ, Khatri R, and DJ Ferguson Jr. 2026. Tetramethylammonium-dependent methanogenesis from Methanococcoides methylutens Q3c requires a nonpyrrolysine monomethylamine methyltransferase homolog. Front. Microbiol. 17:1739651. https://doi.org/10.3389/fmicb.2026.1739651
Picking J, Li Y, Ticak T, Ferguson DJ Jr., Hao B, and Krzycki JA. 2026. Delineation of the Active Site of MtgB, a Cobalamin-dependent Glycine Betaine Methyltransferase. J. Biol. Chem. https://doi.org/10.1016/j.jbc.2026.111216
Timsina R, Gora RA, and DJ Ferguson Jr. 2025. Proteomic and metabolomic analysis reveals new insights into quaternary amine metabolism in Citrobacter amalonaticus CJ25. mSphere. 10(9):e0042125: 100157. https://doi.org/10.1128/msphere.00421-25.
Kashyap JS, Ringiesn JR, Schwab N, and DJ Ferguson Jr. 2022. Isolation and characterization of a novel choline degrading Citrobacter amalonaticus strain from the human gut. Curr. Res. Microb. Sci. 3: 100157. https://doi.org/10.1016/j.crmicr.2022.100157
Creighbaum AJ, Ticak T, Shinde S, Wang X, and DJ Ferguson Jr. 2019. Examination of the glycine betaine-dependent methylotrophic methanogenesis pathway: insights into anaerobic quaternary amine methylotrophy. Front. Microbiol. 10:2572. https://doi.org/10.3389/fmicb.2019.02572
Ticak T, Kuntz, D, Girosky K, Krzycki J.A., and D.J. Ferguson Jr. 2014. A nonpyrrolysine member of the widely distributed trimethylamine methyltransferase family is a glycine betaine methyltransferase. Proc. Nat. Acad. Sci. U.S.A. Oct 28; 111(43):E4668-76. https://www.pnas.org/doi/full/10.1073/pnas.1409642111
Ticak T, Hariraju D, Bayron M, Arivett B.A., Fiester S.E., and D.J. Ferguson Jr. 2014. Isolation and characterization of a tetramethylammonium degrading Methanococcoides strain and a novel glycine betaine utilizing Methanolobus strain. Arch. Microbiol. 197(2): 97-209. https://doi.org/10.1007/s00203-014-1043-6
