Pseudomonas aeruginosa PqsA Is an Anthranilate-Coenzyme A Ligase

dc.contributor.authorColeman, James P.en_US
dc.contributor.authorHudson, L. Lynnen_US
dc.contributor.authorMcKnight, Susan L.en_US
dc.contributor.authorFarrow, John M. IIIen_US
dc.contributor.authorCalfee, M. Worthen_US
dc.contributor.authorLindsey, Claire A.en_US
dc.contributor.authorPesci, Everett C.en_US
dc.date.accessioned2011-02-17T16:31:26Zen_US
dc.date.accessioned2011-05-17T01:40:09Z
dc.date.available2011-02-17T16:31:26Zen_US
dc.date.available2011-05-17T01:40:09Z
dc.date.issued2008-02en_US
dc.description.abstractPseudomonas 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. Originally published Journal of Bacteriology, Vol. 190, No. 4, Feb 2008en_US
dc.identifier.citationJournal of Bacteriology; 190:4 p. 1247-1255en_US
dc.identifier.pmidPMC2238192en_US
dc.identifier.urihttp://hdl.handle.net/10342/3250en_US
dc.language.isoen_USen_US
dc.publisherEast Carolina Universityen_US
dc.relation.urihttp://jb.asm.org/cgi/content/abstract/190/4/1247en_US
dc.rightsAuthor notified of opt-out rights by Cammie Jennings prior to upload of this article.en_US
dc.subjectPseudomonas aeruginosaen_US
dc.subjectVirulence regulationen_US
dc.subjectQuinolone signalingen_US
dc.titlePseudomonas aeruginosa PqsA Is an Anthranilate-Coenzyme A Ligaseen_US
dc.typeArticleen_US

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