scholarly journals Amelioration of Cryptosporidium parvum Infection In Vitro and In Vivo by Targeting Parasite Fatty Acyl-Coenzyme A Synthetases

2013 ◽  
Vol 209 (8) ◽  
pp. 1279-1287 ◽  
Author(s):  
F. Guo ◽  
H. Zhang ◽  
J. M. Fritzler ◽  
S. D. Rider ◽  
L. Xiang ◽  
...  
Keyword(s):  
Cryptosporidium Parvum ◽  
Coenzyme A ◽  
Fatty Acyl ◽  
Acyl Coenzyme A

scholarly journals Pseudomonas aeruginosa PqsA Is an Anthranilate-Coenzyme A Ligase

2007 ◽  
Vol 190 (4) ◽  
pp. 1247-1255 ◽  
Author(s):  
James P. Coleman ◽  
L. Lynn Hudson ◽  
Susan L. McKnight ◽  
John M. Farrow ◽  
M. Worth Calfee ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Coenzyme A ◽  
Intercellular Signaling ◽  
Signaling Systems ◽  
Coa Ligase ◽  
Coenzyme A Ligase ◽  
Opportunistic Human Pathogen ◽  
Acyl Coenzyme A

ABSTRACT Pseudomonas aeruginosa is an opportunistic human pathogen which relies on several intercellular signaling systems for optimum population density-dependent regulation of virulence genes. The Pseudomonas quinolone signal (PQS) is a 3-hydroxy-4-quinolone with a 2-alkyl substitution which is synthesized by the condensation of anthranilic acid with a 3-keto-fatty acid. The pqsABCDE operon has been identified as being necessary for PQS production, and the pqsA gene encodes a predicted protein with homology to acyl coenzyme A (acyl-CoA) ligases. In order to elucidate the first step of the 4-quinolone synthesis pathway in P. aeruginosa, we have characterized the function of the pqsA gene product. Extracts prepared from Escherichia coli expressing PqsA were shown to catalyze the formation of anthraniloyl-CoA from anthranilate, ATP, and CoA. The PqsA protein was purified as a recombinant His-tagged polypeptide, and this protein was shown to have anthranilate-CoA ligase activity. The enzyme was active on a variety of aromatic substrates, including benzoate and chloro and fluoro derivatives of anthranilate. Inhibition of PQS formation in vivo was observed for the chloro- and fluoroanthranilate derivatives, as well as for several analogs which were not PqsA enzymatic substrates. These results indicate that the PqsA protein is responsible for priming anthranilate for entry into the PQS biosynthetic pathway and that this enzyme may serve as a useful in vitro indicator for potential agents to disrupt quinolone signaling in P. aeruginosa.

scholarly journals Regulation of Rabbit Intestinal Acyl Coenzyme A-Cholesterol Acyltransferase In Vivo and In Vitro

1982 ◽  
Vol 83 (4) ◽  
pp. 873-880 ◽  
Author(s):  
F. Jeffrey Field ◽  
Allen D. Cooper ◽  
Sandra K. Erickson
Keyword(s):  
Coenzyme A ◽  
Cholesterol Acyltransferase ◽  
Acyl Coenzyme A

In Vitro and in Vivo Studies on Acyl-Coenzyme A-Dependent Bioactivation of Zomepirac in Rats

2005 ◽  
Vol 18 (11) ◽  
pp. 1729-1736 ◽  
Author(s):  
Jørgen Olsen ◽  
Chunze Li ◽  
Inga Bjørnsdottir ◽  
Ulrik Sidenius ◽  
Steen Honoré Hansen ◽  
...  
Keyword(s):  
Coenzyme A ◽  
In Vivo Studies ◽  
Acyl Coenzyme A

scholarly journals Identification by High-Throughput Screening of Pseudomonas Acyl–Coenzyme A Synthetase Inhibitors

2017 ◽  
Vol 22 (7) ◽  
pp. 897-905
Author(s):  
Lorenzo Turcano ◽  
Daniela Visaggio ◽  
Emanuela Frangipani ◽  
Antonino Missineo ◽  
Matteo Andreini ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Coenzyme A ◽  
Firefly Luciferase ◽  
Fatty Acid Binding ◽  
Compound Collection ◽  
Bacterial Fitness ◽  
Acyl Coenzyme A ◽  
Micromolar Range

Pseudomonas infections are common among hospitalized, immunocompromised, and chronic lung disease patients. These infections are recalcitrant to common antibacterial therapies due to inherent antibiotic resistance. To meet the need of new anti- Pseudomonas drugs, a sensitive, homogenous, and robust assay was developed with the aim of identifying inhibitors of acyl–coenzyme A synthetases (ACSs) from Pseudomonas. Given the importance of fatty acids for in vivo nutrition of Pseudomonas, such inhibitors might have the potential to reduce the bacterial fitness during infection. The assay, based on a coupled reaction between the Pseudomonas spp. ACS and the firefly luciferase, allowed the identification of three classes of inhibitors by screening of a diverse compound collection. These compounds were confirmed to reversibly bind ACS with potencies in the micromolar range. Two classes were found to compete with acyl–coenzyme A, while the third one was competitive with fatty acid binding. Although these compounds inhibit the bacterial ACS in cell-free assays, they show modest or no effect on Pseudomonas growth in vitro.

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