title: Pseudomonas aeruginosa autoinducer modulates host cell responses through calcium signalling.
abstract: The opportunistic pathogen Pseudomonas aeruginosa utilizes a cell density-dependent signalling phenomenon known as quorum sensing (QS) to regulate several virulence factors needed for infection. Acylated homoserine lactones, or autoinducers, are the primary signal molecules that mediate QS in P. aeruginosa. The autoinducer N-3O-dodecanoyl-homoserine lactone (3O-C12) exerts effects on mammalian cells, including upregulation of pro-inflammatory mediators and induction of apoptosis. However, the mechanism(s) by which 3O-C12 affects mammalian cell responses is unknown. Here we report that 3O-C12 induces apoptosis and modulates the expression of immune mediators in murine fibroblasts and human vascular endothelial cells (HUVEC). The effects of 3O-C12 were accompanied by increases in cytosolic calcium levels that were mobilized from intracellular stores in the endoplasmic reticulum (ER). Calcium release was blocked by an inhibitor of phospholipase C, suggesting that release occurred through inositol triphosphate (IP3) receptors in the ER. Apoptosis, but not immunodulatory gene activation, was blocked when 3O-C12-exposed cells were co-incubated with inhibitors of calcium signalling. This study indicates that 3O-C12 can activate at least two independent signal transduction pathways in mammalian cells, one that involves increases in intracellular calcium levels and leads to apoptosis, and a second pathway that results in modulation of the inflammatory response.
authors.affiliation: Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
authors.forename: E K
authors.initials: EK
authors.lastname: Shiner
authors.forename: D
authors.initials: D
authors.lastname: Terentyev
authors.forename: A
authors.initials: A
authors.lastname: Bryan
authors.forename: S
authors.initials: S
authors.lastname: Sennoune
authors.forename: R
authors.initials: R
authors.lastname: Martinez-Zaguilan
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Gyorke
authors.forename: S C
authors.initials: SC
authors.lastname: Williams
authors.forename: K P
authors.initials: KP
authors.lastname: Rumbaugh
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D020013:Calcium Signaling; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; C109860:N-(3-oxododecanoyl)homoserine lactone; D037521:Virulence Factors; D006714:Homoserine; D015107:4-Butyrolactone