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Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa
Published on: June 30, 2016
Pseudomonas aeruginosa autoinducer modulates host cell responses through calcium signalling
E K Shiner1, D Terentyev, A Bryan
1Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Cellular Microbiology
|September 21, 2006
Summary
Pseudomonas aeruginosa uses quorum sensing (QS) autoinducers like 3O-C12 to trigger apoptosis and alter immune responses in mammalian cells. This involves calcium signaling, revealing dual pathways for virulence factor regulation.
Area of Science:
- Microbiology and Immunology
- Cellular and Molecular Biology
Background:
- Pseudomonas aeruginosa employs quorum sensing (QS) for virulence, using autoinducers like N-3O-dodecanoyl-homoserine lactone (3O-C12).
- The precise mechanisms by which 3O-C12 impacts mammalian cells remain largely unknown.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying 3O-C12's effects on mammalian cells.
- To investigate the role of intracellular calcium signaling in 3O-C12-induced responses.
Main Methods:
- Treatment of murine fibroblasts and human umbilical vein endothelial cells (HUVECs) with 3O-C12.
- Measurement of cytosolic calcium levels and assessment of apoptosis induction.
- Pharmacological inhibition of phospholipase C and calcium signaling pathways.
Main Results:
- 3O-C12 induced apoptosis and modulated immune mediator expression in both cell types.
- Elevated cytosolic calcium, originating from endoplasmic reticulum stores via IP3 receptors, accompanied 3O-C12 effects.
- Calcium signaling inhibition blocked 3O-C12-induced apoptosis but not immunomodulatory gene activation.
Conclusions:
- 3O-C12 activates distinct signaling pathways in mammalian cells.
- One pathway involves calcium mobilization leading to apoptosis.
- A second, calcium-independent pathway modulates the inflammatory response.
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