Michael R. McNeil
Professor

Phone: 491-1784
Fax: 491-1815
Email: M.McNeil@colostate.edu
Office: A2A Microbiology Building
Lab: A2 Microbiology Building

Degrees

B.S., Allegheny College
M.S., Massachusetts Institute of Technology
Ph.D., University of Colorado

Research Interests

Mycobacteria Cell Envelope: Drug targeting, Biosynthesis, and Endogenous Degradation

Our major research goal is the development of new drugs against M. tuberculosis. Our target for new drugs is the unique cell envelope of mycobacteria. The research is proceeding on both an applied and a basic research track. On the applied track we are screening for inhibitors enzymes essential for M. tuberculosis cell wall synthesis, namely the enzymes that form dTDP-rhamnose, UDP-Galf, and UDP-GlcNAc. These inhibitors are tested for their ability to kill M. tuberculosis cells growing in culture and supplied to collaborators to incorporate into crystal structures of the relevant enzymes and to a medicinal chemist collaborator to make addition compounds. Compounds that do well against M. tuberculosis in culture are then tested in mice by Dr. Lenaerts of this department. On the basic research side we are studying the sugar transferases that use the sugar nucleotides above to build the cell wall as well as the enzymes that form the arabinofuranose residues of the cell wall. Also, enzymes that degrade the cell wall, both the cell wall arabinan and cell wall peptidoglycan, are being studied with the ultimate goal of developing drugs that stimulate cell wall degradation.

Selected Publications

Pub Med for McNeil MR.

Scherman, M. S., K. Winans, C. R. Bertozzi, R. Stern, V. C. Jones, and M. R. McNeil. 2003. Drug targeting Mycobacterium tuberculosis cell wall synthesis: development of a microtiter plate-based screen for UDP-galactopyranose mutase and identification of an inhibitor from a uridine-based library. Antimicrob.Agents Chemother. 47:378-382.

Babaoglu K, Page MA, Jones VC, McNeil MR, Dong C, Naismith JH, Lee RE Novel inhibitors of an emerging target in Mycobacterium tuberculosis;substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis.Bioorg Med Chem Lett. 2003 Oct 16;13(19):3227-3230

Ma, Yufang, Fei Pan, and Michael McNeil. 2002. The formation of dTDP-rhamnose is essential for growth of mycobacteria. J. Bacteriol. 184: 3392-3395.

Yufang Ma, Richard J. Stern, Michael S. Scherman, Varalakshmi D. Vissa, Wenxin Yan, Victoria Cox Jones, Fangqiu Zhang, Scott G. Franzblau, Walter H. Lewis, and Michael R. McNeil. 2001. Drug Targeting M. tuberculosis Cell Wall Synthesis: The Genetics of dTDP-Rhamnose Synthetic Enzymes and Development of a Microtiter Plate Based Screen for Inhibitors of the Conversion of dTDP-Glucose to dTDP-Rhamnose. Antimicrob.Agents Chemother. 45: 1407-1416

Pan, Fei, Mary Jackson, Yufang Ma, and Michael McNeil. 2001. Determination that cell wall galactofuran synthesis is essential for growth of mycobacteria. J. Bacteriol. 183: 3991-3998.

Escuyer, V. E., M. A. Lety, J. B. Torrelles, K. H. Khoo, J. B. Tang, C. D. Rithner, C. Frehel, M. R. McNeil, P. J. Brennan , and D. Chatterjee. 2001. The role of the embA and embB gene products in the biosynthesis of the terminal hexaarabinofuranosyl motif of Mycobacterium smegmatis arabinogalactan. J.Biol.Chem. 276:48854-48862.

Xin, Y., Y. Huang, and M.R. McNeil. 1999. The presence of an endogenous endo-D-arabinase in Mycobacterium smegmatis and characterization of its oligoarabinoside product. Biochim. Biophys. Acta 1473:267-271.

McNeil, M.R. 1999. Arabinogalactan in mycobacteria: structure, biosynthesis, and genetics. J. Goldberg. (ed.), Genetics of bacterial polysaccharides. CRC Press, Boca Raton, FL.

Scherman, M.S., L. Kalbe-Bournonville, D. Bush, Y. Xin, and M. McNeil. 1996. Polyprenylphosphate-pentoses in mycobacteria are synthesized from phosphoribose pyrophosphate. J. Biol. Chem. 271:29652029658.