ArticleThe Journal of biological chemistry2012
Pseudomonas aeruginosa exotoxin Y is a promiscuous cyclase that increases endothelial tau phosphorylation and permeability.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 105 citations in OpenAlex.
- Molecular Mechanisms Underlying the Pathogenicity ofMedicina (Kaunas, Lithuania) · 2026Review
- Role of the intestinal microbiota in sepsis-associated encephalopathy.Burns & trauma · 2026Review
- Interplay between T3SS effectors, ExoY activation, and cGMP signaling in Pseudomonas aeruginosa infection.Nature communications · 2025Article
- The interaction between dysfunction of vasculature and tauopathy in Alzheimer's disease and related dementias.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Article
- cUMP elicits interendothelial gap formation duringAmerican journal of physiology. Lung cellular and molecular physiology · 2024Article
- Lung endothelium, tau, and amyloids in health and disease.Physiological reviews · 2024Review
- Oh my gut! Is the microbial origin of neurodegenerative diseases real?Infection and immunity · 2023Review
- Gamma secretase activating protein promotes end-organ dysfunction after bacterial pneumonia.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Infection promotes Ser-214 phosphorylation important for generation of cytotoxic tau variants.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunction in a mouse model of tauopathy.Nature communications · 2023Article
- Current concepts on Pseudomonas aeruginosa interaction with human airway epithelium.PLoS pathogens · 2023Review
- What the Gut Tells the Brain-Is There a Link between Microbiota and Huntington's Disease?International journal of molecular sciences · 2023Review
- Significance of Pulmonary Endothelial Injury and the Role of Cyclooxygenase-2 and Prostanoid Signaling.Bioengineering (Basel, Switzerland) · 2023Review
- Review
- A Robust and Sensitive Spectrophotometric Assay for the Enzymatic Activity of Bacterial Adenylate Cyclase Toxins.Toxins · 2022Article
- Bacterial Nucleotidyl Cyclases Activated by Calmodulin or Actin in Host Cells: Enzyme Specificities and Cytotoxicity Mechanisms Identified to Date.International journal of molecular sciences · 2022Review
- Molecular Mechanisms Involved in Pseudomonas aeruginosa Bacteremia.Advances in experimental medicine and biology · 2022Review
- Neurovascular Dysfunction in Diverse Communities With Health Disparities-Contributions to Dementia and Alzheimer's Disease.Frontiers in neuroscience · 2022Review
- Mechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens.Nature communications · 2021Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Exotoxin Y (ExoY) is a type III secretion system effector found in ~ 90% of the Pseudomonas aeruginosa isolates. Although it is known that ExoY causes inter-endothelial gaps and vascular leak, the mechanisms by which this occurs are poorly understood. Using both a bacteria-delivered and a codon-optimized conditionally expressed ExoY, we report that this toxin is a dual soluble adenylyl and guanylyl cyclase that results in intracellular cAMP and cGMP accumulation. The enzymatic activity of ExoY caused phosphorylation of endothelial Tau serine 214, accumulation of insoluble Tau, inter-endothelial cell gap formation, and increased macromolecular permeability. To discern whether the cAMP or cGMP signal was responsible for Tau phosphorylation and barrier disruption, pulmonary microvascular endothelial cells were engineered for the conditional expression of either wild-type guanylyl cyclase, which synthesizes cGMP, or a mutated guanylyl cyclase, which synthesizes cAMP. Sodium nitroprusside stimulation of the cGMP-generating cyclase resulted in transient Tau serine 214 phosphorylation and gap formation, whereas stimulation of the cAMP-generating cyclase induced a robust increase in Tau serine 214 phosphorylation, gap formation, and macromolecular permeability. These results indicate that the cAMP signal is the dominant stimulus for Tau phosphorylation. Hence, ExoY is a promiscuous cyclase and edema factor that uses cAMP and, to some extent, cGMP to induce the hyperphosphorylation and insolubility of endothelial Tau. Because hyperphosphorylated and insoluble Tau are hallmarks in neurodegenerative tauopathies such as Alzheimer disease, acute Pseudomonas infections cause a pathophysiological sequela in endothelium previously recognized only in chronic neurodegenerative diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.