My laboratory has been active in an ongoing collaboration
with the laboratory of Dr. Everett C. Pesci, focused on the pathway of
biosynthesis of the Pseudomonas Quinolone Signal (PQS) and the mechanism by
which it regulates virulence gene expression. This PQS signal molecule PQS, 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
Another research area we continue to pursue is on the
characterization of bacteria and enzymes involved in the intestinal and
environmental metabolism of bile acids and steroids.
PublicationsJ.P. Coleman, L.L. Hudson, and M.J. Adams. 1994.
Characterization and regulation of the NADP-linked 7(alpha)-hydroxysteroid
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.
L.C. Kirby, R.A. Klein, J.P. Coleman. 1995. Continuous
spectrophotometric assay of conjugated bile acid hydrolase. Lipids. 30:863-867
Rocha, ER, T Selby, JP Coleman, and CJ Smith. 1996.
The oxidative stress response in an anaerobe, Bacteroides fragilis: A role
for catalase in protection against hydrogen peroxide. J. Bacteriol. 178:6895-6903
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.
Bennett M.J., S.L. McKnight, and J.P. Coleman. 2003.
Cloning and characterization of the 7α-hydroxysteroid dehydrogenase from Bacteroides fragilis. Current
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
Coleman JP, LL Hudson, SL McKnight, JM Farrow 3rd, MW
Calfee, CA Lindsey, and EC Pesci.
2008. Pseudomonas aeruginosa
PqsA is an anthranilate-coenzyme A ligase.
J. Bacteriol. 190:1247-1255.
Farrow JM 3rd, ZM Sund, ML Ellison, DS Wade, JP Coleman,
and EC Pesci. 2008. PqsE functions independently of PqsR-Pseudomonas quinolone signal and
enhances the rhl quorum-sensing system.
J. Bacteriol. 190:7043–7051.
Bera AK, V Atanasova, H Robinson, E Eisenstein, JP
Coleman, EC Pesci, and JF Parsons.
2009. Structure of PqsD, a Pseudomonas quinolone signal
biosynthetic enzyme, in complex with anthranilate. Biochemistry 48(36):8644-8655.
Knoten CA, Hudson LL, Coleman JP, Farrow JM 3rd, Pesci
EC. 2011. KynR, a Lrp/AsnC-type transcriptional
regulator, directly controls the kynurenine pathway in Pseudomonas aeruginosa. J. Bacteriol. 193:6567-6575.
Tipton KA, Coleman JP, Pesci EC. 2013.
QapR (PA5506) represses an operon that negatively affects PQS in Pseudomonas aeruginosa. J.
Knoten CA, Wells G, Coleman JP, Pesci EC. 2014.
A conserved suppressor mutation in a tryptophan auxotroph results in
dysregulation of Pseudomonas
quinolone signal synthesis. J. Bacteriol. 196:2413-2422.
Tipton KA, Coleman JP, Pesci EC. Post-transcriptional
regulation of gene PA5507 controls PQS concentration in Pseudomonas aeruginosa.
2015. Mol. Microbiol. 96:670-683.
Farrow JM 3rd, Hudson LL, Wells G, Coleman JP, Pesci
EC. 2015. CysB Negatively Affects the Transcription of
pqsR and Pseudomonas Quinolone Signal Production in Pseudomonas aeruginosa. J
Ji C,Sharma I, Pratihar D, Hudson LL, Maura D, Guney
T, Rahme LG, Pesci EC, Coleman JP, Tan DS.
2016. Designed small-molecule inhibitors
of the anthranilyl-CoA synthetase PqsA block quinolone biosynthesis in Pseudomonas aeruginosa. ACS Chem Biol (in press)