My laboratory has been active in studying the regulation and enzymology of enzymes involved in the metabolism of bile acids and steroids by human intestinal bacteria.  This work has included the elucidation of pathways involved in the metabolism of these compounds by bacteria and by liver enzymes.  This interest has led to an ongoing collaboration with the laboratory of Dr. Everett C. Pesci, in which the focus of my laboratory is to elucidate the pathway of biosynthesis of the Pseudomonas Quinolone Signal (PQS).  This signal molecule, 2-heptyl-3-hydroxy-4-quinolone, is produced by Pseudomonas aeruginosa and plays a central role in the regulation of numerous virulence factors in this organism which enable it to cause infections in plants, insects, and animals.  Our work currently is focused on the pqsABCDE operon, specifically, the pqsA gene product, which we have determined to be an anthranilic acid – coenzyme A ligase.  We are currently studying the kinetic and structural properties of this enzyme to identify potential inhibitors of the reaction and also to facilitate studies on the other gene products of the pqsABCDE operon.  Our long term goal is to identify PQS-biosynthetic steps that can be targeted for disruption by specific antimicrobial compounds.

Coleman, J.P., W.B. White, B. Egestad, J. Sjövall and P.B. Hylemon.  1987. Biosynthesis of a novel bile acid nucleotide by a 7α-dehydroxylating intestinal Eubacterium species.  J. Biol. Chem.  262:4701-4707.

J.P. Coleman, L.L. Hudson, and M.J. Adams. 1994. Characterization and regulation of the NADP-linked 7(alpha)-hydroxysteroid dehydroxysteroid dehydrogenase gene from Clostridium sordellii. Journal of Bacteriology. 176:4865-4874.

J.P. Coleman, L.C. Kirby, and R.A. Klein. 1995. Synthesis and characterization of novel analogs of conjugated bile acids containing reversed amide bonds. Journal of Lipid Research. 36:901-910.

J.P. Coleman and L.L. Hudson. 1995. Cloning and characterization of a conjugated bile acid hydrolase from Clostridium perfringens. Applied and Environmental Microbiology. 61:2514-2520.

L.C. Kirby, R.A. Klein, J.P. Coleman. 1995. Continuous spectrophotometric assay of conjugated bile acid hydrolase. Lipids. 30:863-867.

J.P. Coleman, L.C. Kirby, K.D.R. Setchell KD., P.B. Hylemon, M. Pandak, D.M. Heuman, and Z.R. Vlahcevic. 1998. Metabolic fate and hepatocyte toxicity of reverse amide analogs of conjugated ursodeoxycholate in the rat. Journal of Steroid Biochemistry and Molecular Biology. 64:91-101

Calfee, M.W., J.P. Coleman, and E.C. Pesci.  2001.  Interference with Pseudomonas quinolone signal synthesis inhibits virulence factor expression by Pseudomonas aeruginosa. Proceedings of the National Academy of Sciences, USA. 98:11633-11637.

Bennett M.J., S.L. McKnight, and J.P. Coleman.  2003.  Cloning and characterization of the 7α-hydroxysteroid dehydrogenase from Bacteroides fragilis.  Current Microbiology 47(6):475-484.

Rossocha M., R. Schultz-Heienbrok,  H. von Moeller,  J.P. Coleman, and W. Saenger.  2005.  Conjugated bile acid hydrolase is a tetrameric N-terminal thiol hydrolase with specific recognition of its cholyl but not of its tauryl product.  Biochemistry 44(15):5739-5748.

Wade D.S., M.W. Calfee, E.R. Rocha, E.A. Ling, E. Engstrom, J.P. Coleman, and E.C. Pesci. 2005.  Regulation of PQS synthesis in Pseudomonas aeruginosa.  Journal of Bacteriology. 187: 4372–4380.