1887

Abstract

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 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. possesses two functional anthranilate synthases, TrpEG and PhnAB, and these enzymes are not functionally redundant, as mutants are tryptophan auxotrophs but produce PQS while mutants in 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 and 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, was shown to be expressed primarily during low-density growth while was expressed primarily at high density. Furthermore, dysregulation of expression eliminated tryptophan auxotrophy in the mutant. Based on these data, we propose a model for anthranilate sequestration by differential transcriptional regulation of the two anthranilate synthase enzymes.

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2013-05-01
2020-01-17
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