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Zusammenfassung: <jats:title>ABSTRACT</jats:title> <jats:p> Cyclic AMP (cAMP) is an important second messenger signaling molecule that controls a wide variety of eukaryotic and prokaryotic responses to extracellular cues. For cAMP-dependent signaling pathways to be effective, the intracellular cAMP concentration is tightly controlled at the level of synthesis and degradation. In the opportunistic human pathogen <jats:italic>Pseudomonas aeruginosa</jats:italic> , cAMP is a key regulator of virulence gene expression. To better understand the role of cAMP homeostasis in this organism, we identified and characterized the enzyme CpdA, a putative cAMP phosphodiesterase. We demonstrate that CpdA possesses 3′,5′-cAMP phosphodiesterase activity <jats:italic>in vitro</jats:italic> and that it utilizes an iron-dependent catalytic mechanism. Deletion of <jats:italic>cpdA</jats:italic> results in the accumulation of intracellular cAMP and altered regulation of <jats:italic>P. aeruginosa</jats:italic> virulence traits. Further, we demonstrate that the cAMP-dependent transcription factor Vfr directly regulates <jats:italic>cpdA</jats:italic> expression in response to intracellular cAMP accumulation, thus providing a feedback mechanism for controlling cAMP levels and fine-tuning virulence factor expression. </jats:p>
Umfang: 2779-2790
ISSN: 0021-9193
1098-5530
DOI: 10.1128/jb.00168-10