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Modulation of the cAMP pathway by Pseudomonas aeruginosa quorum sensing molecules
Author(s) -
Stoddart Leigh,
Coward William,
Williams Paul,
Hill Steve
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.656.4
Subject(s) - quorum sensing , pseudomonas aeruginosa , forskolin , rolipram , phosphodiesterase , second messenger system , cyclic adenosine monophosphate , pertussis toxin , signal transduction , phosphorylation , camp dependent pathway , microbiology and biotechnology , chemistry , receptor , cell signaling , biofilm , homoserine , virulence , biology , biochemistry , g protein , enzyme , bacteria , gene , genetics
Pseudomonas aeruginosa (PA) uses quorum sensing molecules (QSMs) to coordinate the production of its virulence factors. These QSMs have also been shown to induce responses within the host mammalian cells. We have investigated the ability of two QSMs, the P. aeruginosa quinolone signal (PQS) and N ‐3‐(oxododecanoyl)‐L‐homoserine lactone (OdDHL), to stimulate a variety of second messenger pathways within HEK293 cells. Both QSMs had little effect upon calcium release or ERK1/2 phosphorylation. In contrast, when examining basal cAMP levels it was found that PQS had minimal effects but OdDHL caused a marked decrease in the cAMP levels in a concentration dependent manner. Both PQS and OdDHL stimulated a decrease in forskolin stimulated cAMP, with PQS having effects at lower concentrations than OdDHL. This was also true when stimulating cAMP production via adenosine or β‐adrenergic receptors endogenously expressed in these cells. Pertussis toxin treatment was unable to alter the effects on cAMP modulated by PQS and OdDHL suggesting that Gα i/o proteins are not directly involved. Interestingly the phosphodiesterase 4 (PDE4) inhibitor rolipram caused a moderate reversal in the QSM simulated inhibition of cAMP levels. Understanding the effects of QSMs upon the cAMP pathway may uncover a novel target for the treatment of PA infections. This work was supported by a University of Nottingham Bridging the Gaps award.