In Vitro and In Vivo Characterization of the Pseudomonas aeruginosa Cyclic AMP (cAMP) Phosphodiesterase CpdA, Required for cAMP Homeostasis and Virulence Factor Regulation

Erin L Fuchs; Evan D Brutinel; Erich R Klem; Anthony R Fehr; Timothy L Yahr; Matthew C Wolfgang

doi:10.1128/JB.00168-10

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In Vitro and In Vivo Characterization of the Pseudomonas aeruginosa Cyclic AMP (cAMP) Phosphodiesterase CpdA, Required for cAMP Homeostasis and Virulence Factor Regulation

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In Vitro and In Vivo Characterization of the Pseudomonas aeruginosa Cyclic AMP (cAMP) Phosphodiesterase CpdA, Required for cAMP Homeostasis and Virulence Factor Regulation

Erin L Fuchs, Evan D Brutinel, Erich R Klem, Anthony R Fehr, Timothy L Yahr and Matthew C Wolfgang

Journal of bacteriology, Vol.192(11), pp.2779-2790

06/2010

DOI: 10.1128/JB.00168-10

PMCID: PMC2876501

PMID: 20348254

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Abstract

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 Pseudomonas aeruginosa , 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 in vitro and that it utilizes an iron-dependent catalytic mechanism. Deletion of cpdA results in the accumulation of intracellular cAMP and altered regulation of P. aeruginosa virulence traits. Further, we demonstrate that the cAMP-dependent transcription factor Vfr directly regulates cpdA expression in response to intracellular cAMP accumulation, thus providing a feedback mechanism for controlling cAMP levels and fine-tuning virulence factor expression.

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Title: Subtitle: In Vitro and In Vivo Characterization of the Pseudomonas aeruginosa Cyclic AMP (cAMP) Phosphodiesterase CpdA, Required for cAMP Homeostasis and Virulence Factor Regulation
Creators: Erin L Fuchs - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Evan D Brutinel - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Erich R Klem - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Anthony R Fehr - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Timothy L Yahr - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Matthew C Wolfgang - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599
Resource Type: Journal article
Publication Details: Journal of bacteriology, Vol.192(11), pp.2779-2790
DOI: 10.1128/JB.00168-10
PMID: 20348254
PMCID: PMC2876501
NLM abbreviation: J Bacteriol
ISSN: 0021-9193
eISSN: 1098-5530
Publisher: American Society for Microbiology (ASM)
Language: English
Date published: 06/2010
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001136902771

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