ArticleThe Journal of biological chemistry2010
Pseudomonas aeruginosa Homoserine lactone activates store-operated cAMP and cystic fibrosis transmembrane regulator-dependent Cl- secretion by human airway epithelia.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Pseudomonas aeruginosa 3-oxo-C12HSL-induced apoptosis involves bitter taste receptor T2R14 and the mitochondrial calcium uniporter.Cell calcium · 2026Article
- Protective role of CFTR during fungal infection of cystic fibrosis bronchial epithelial cells withFrontiers in cellular and infection microbiology · 2023Article
- Environmental, Microbiological, and Immunological Features of Bacterial Biofilms Associated with Implanted Medical Devices.Clinical microbiology reviews · 2022Review
- Pharmacology of T2R Mediated Host-Microbe Interactions.Handbook of experimental pharmacology · 2022Article
- Impact ofFrontiers in immunology · 2020Review
- Calcium Regulation of Bacterial Virulence.Advances in experimental medicine and biology · 2020Review
- The cAMP Pathway Amplifies Early MyD88-Dependent and Type I Interferon-Independent LPS-Induced Interleukin-10 Expression in Mouse Macrophages.Mediators of inflammation · 2019Article
- N-(3-Oxo-acyl)-homoserine lactone induces apoptosis primarily through a mitochondrial pathway in fibroblasts.Cellular microbiology · 2018Article
- Aspects of Gut Microbiota and Immune System Interactions in Infectious Diseases, Immunopathology, and Cancer.Frontiers in immunology · 2018Review
- The Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor Augments Mucociliary Clearance Abrogating Cystic Fibrosis Transmembrane Conductance Regulator Inhibition by Cigarette Smoke.American journal of respiratory cell and molecular biology · 2017Article
- "Store-operated" cAMP signaling contributes to Ca2+-activated Cl- secretion in T84 colonic cells.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Paraoxonase 2 serves a proapopotic function in mouse and human cells in response to the Pseudomonas aeruginosa quorum-sensing molecule N-(3-Oxododecanoyl)-homoserine lactone.The Journal of biological chemistry · 2015Article
- Modulation of Host Biology by Pseudomonas aeruginosa Quorum Sensing Signal Molecules: Messengers or Traitors.Frontiers in microbiology · 2015Review
- Pseudomonas aeruginosa quorum-sensing molecule homoserine lactone modulates inflammatory signaling through PERK and eI-F2α.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Pseudomonas aeruginosa homoserine lactone triggers apoptosis and Bak/Bax-independent release of mitochondrial cytochrome C in fibroblasts.Cellular microbiology · 2014Article
- Thapsigargin blocks Pseudomonas aeruginosa homoserine lactone-induced apoptosis in airway epithelia.American journal of physiology. Cell physiology · 2014Article
- Small molecule screen yields inhibitors of Pseudomonas homoserine lactone-induced host responses.Cellular microbiology · 2014Article
- The bacterial quorum-sensing signal molecule N-3-oxo-dodecanoyl-L-homoserine lactone reciprocally modulates pro- and anti-inflammatory cytokines in activated macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- X-box binding protein 1 (XBP1s) is a critical determinant of Pseudomonas aeruginosa homoserine lactone-mediated apoptosis.PLoS pathogens · 2013Article
- Termination and activation of store-operated cyclic AMP production.Journal of cellular and molecular medicine · 2012Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
The ubiquitous bacterium Pseudomonas aeruginosa frequently causes hospital-acquired infections. P. aeruginosa also infects the lungs of cystic fibrosis (CF) patients and secretes N-(3-oxo-dodecanoyl)-S-homoserine lactone (3O-C12) to regulate bacterial gene expression critical for P. aeruginosa persistence. In addition to its effects as a quorum-sensing gene regulator in P. aeruginosa, 3O-C12 elicits cross-kingdom effects on host cell signaling leading to both pro- or anti-inflammatory effects. We find that in addition to these slow effects mediated through changes in gene expression, 3O-C12 also rapidly increases Cl(-) and fluid secretion in the cystic fibrosis transmembrane regulator (CFTR)-expressing airway epithelia. 3O-C12 does not stimulate Cl(-) secretion in CF cells, suggesting that lactone activates the CFTR. 3O-C12 also appears to directly activate the inositol trisphosphate receptor and release Ca(2+) from the endoplasmic reticulum (ER), lowering [Ca(2+)] in the ER and thereby activating the Ca(2+)-sensitive ER signaling protein STIM1. 3O-C12 increases cytosolic [Ca(2+)] and, strikingly, also cytosolic [cAMP], the known activator of CFTR. Activation of Cl(-) current by 3O-C12 was inhibited by a cAMP antagonist and increased by a phosphodiesterase inhibitor. Finally, a Ca(2+) buffer that lowers [Ca(2+)] in the ER similar to the effect of 3O-C12 also increased cAMP and I(Cl). The results suggest that 3O-C12 stimulates CFTR-dependent Cl(-) and fluid secretion in airway epithelial cells by activating the inositol trisphosphate receptor, thus lowering [Ca(2+)] in the ER and activating STIM1 and store-operated cAMP production. In CF airways, where CFTR is absent, the adaptive ability to rapidly flush the bacteria away is compromised because the lactone cannot affect Cl(-) and fluid secretion.
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Registered trials
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