ArticleInfection and immunity2009
Processing of Pseudomonas aeruginosa exotoxin A is dispensable for cell intoxication.
Article in Infection and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Review
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- Revisiting Host-Pathogen Interactions in Cystic Fibrosis Lungs in the Era of CFTR Modulators.International journal of molecular sciences · 2023Review
- Strategies to mitigate the on- and off-target toxicities of recombinant immunotoxins: an antibody engineering perspective.Antibody therapeutics · 2022Review
- ABToxins · 2022Review
- Potential Therapeutic Targets for Combination Antibody Therapy againstAntibiotics (Basel, Switzerland) · 2021Review
- Preparation and evaluation of the exotoxin A nano-gold conjugate as a vaccine candidate forIranian journal of basic medical sciences · 2021Article
- Cell Death Signaling Pathway Induced by Cholix Toxin, a Cytotoxin and eEF2 ADP-Ribosyltransferase Produced byToxins · 2020Review
- Phenazines as potential biomarkers of Pseudomonas aeruginosa infections: synthesis regulation, pathogenesis and analytical methods for their detection.Analytical and bioanalytical chemistry · 2020Review
- Cholix toxin, an eukaryotic elongation factor 2 ADP-ribosyltransferase, interacts with Prohibitins and induces apoptosis with mitochondrial dysfunction in human hepatocytes.Cellular microbiology · 2019Article
- Article
- Cargo-delivery platforms for targeted delivery of inhibitor cargos against botulism.Current topics in medicinal chemistry · 2014Review
- The apoptogenic toxin AIP56 is a metalloprotease A-B toxin that cleaves NF-κb P65.PLoS pathogens · 2013Article
- A recombinant immunotoxin against the tumor-associated antigen mesothelin reengineered for high activity, low off-target toxicity, and reduced antigenicity.Molecular cancer therapeutics · 2013Article
- The 1.8 Å cholix toxin crystal structure in complex with NAD+ and evidence for a new kinetic model.The Journal of biological chemistry · 2012Article
- Reductive activation of type 2 ribosome-inactivating proteins is promoted by transmembrane thioredoxin-related protein.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exotoxin A is a major virulence factor of Pseudomonas aeruginosa. This toxin binds to a specific receptor on animal cells, allowing endocytosis of the toxin. Once in endosomes, the exotoxin can be processed by furin to generate a C-terminal toxin fragment that lacks the receptor binding domain and is retrogradely transported to the endoplasmic reticulum for retrotranslocation to the cytosol through the Sec61 channel. The toxin then blocks protein synthesis by ADP ribosylation of elongation factor 2, thereby triggering cell death. A shorter intracellular route has also been described for this toxin. It involves direct translocation of the entire toxin from endosomes to the cytosol and therefore does not rely on furin-mediated cleavage. To examine the implications of endosomal translocation in the intoxication process, we investigated whether the toxin required furin-mediated processing in order to kill cells. We used three different approaches. We first fused to the N terminus of the toxin proteins with different unfolding abilities so that they inhibited or did not inhibit endosomal translocation of the chimera. We then assayed the amount of toxin fragments delivered to the cytosol during cell intoxication. Finally we used furin inhibitors and examined the fate and intracellular localization of the toxin and its receptor. The results showed that exotoxin cytotoxicity results largely from endosomal translocation of the entire toxin. We found that the C-terminal fragment was unstable in the cytosol.
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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.