title: The role of two Pseudomonas aeruginosa anthranilate synthases in tryptophan and quorum signal production.
abstract: Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that causes infections in the lungs of individuals with the genetic disease cystic fibrosis. Density-dependent production of toxic factors regulated by the Pseudomonas quinolone signal (2-heptyl-3-hydroxy-4-quinolone; PQS) have been proposed to be involved in P. aeruginosa virulence. PQS biosynthesis requires conversion of the central metabolite chorismate to anthranilate by anthranilate synthase. This reaction is also the first step in tryptophan biosynthesis. P. aeruginosa possesses two functional anthranilate synthases, TrpEG and PhnAB, and these enzymes are not functionally redundant, as trpEG mutants are tryptophan auxotrophs but produce PQS while mutants in phnAB are tryptophan prototrophs but do not produce PQS in minimal media. The goal of the work described in this paper was to determine the mechanism for this lack of functional complementation of TrpEG and PhnAB. Our results reveal that overexpression of either enzyme compensates for tryptophan auxotrophy and PQS production in the trpEG and phnAB mutants respectively, leading to the hypothesis that differential regulation of these genes is responsible for the lack of functional complementation. In support of this hypothesis, trpEG was shown to be expressed primarily during low-density growth while phnAB was expressed primarily at high density. Furthermore, dysregulation of phnAB expression eliminated tryptophan auxotrophy in the P. aeruginosa trpEG mutant. Based on these data, we propose a model for anthranilate sequestration by differential transcriptional regulation of the two P. aeruginosa anthranilate synthase enzymes.
authors: Section of Molecular Genetics and Microbiology, The Institute of Cell and Molecular Biology, The University of Texas at Austin, Austin, TX, USA.
authors: Gregory C
authors: GC
authors: Palmer
authors: Section of Molecular Genetics and Microbiology, The Institute of Cell and Molecular Biology, The University of Texas at Austin, Austin, TX, USA.
authors: Peter A
authors: PA
authors: Jorth
authors: Section of Molecular Genetics and Microbiology, The Institute of Cell and Molecular Biology, The University of Texas at Austin, Austin, TX, USA.
authors: Marvin
authors: M
authors: Whiteley
mesh_terms: D000878:Anthranilate Synthase / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D010802:Phylogeny; D011550:Pseudomonas aeruginosa / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D015363:Quinolones / Q000378:metabolism*; D015398:Signal Transduction; D014364:Tryptophan / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015363:Quinolones; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D014364:Tryptophan; D000878:Anthranilate Synthase