ArticlePLoS pathogens2015
Pseudomonas aeruginosa ExoT Induces Atypical Anoikis Apoptosis in Target Host Cells by Transforming Crk Adaptor Protein into a Cytotoxin.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- CCL3 and LPS combination therapy significantly reduces infection and stimulates wound healing in diabetic mice by boosting proinflammatory responses.The Journal of investigative dermatology · 2026Article
- Integrating resistance biology, virulence networks, and precision therapeutics against multidrug-resistant Pseudomonas aeruginosa.Infection · 2026Review
- Molecular Mechanisms Underlying the Pathogenicity ofMedicina (Kaunas, Lithuania) · 2026Review
- Article
- Interplay between T3SS effectors, ExoY activation, and cGMP signaling in Pseudomonas aeruginosa infection.Nature communications · 2025Article
- Carbon source-driven downregulation of the sRNA AmiL enhancesVirulence · 2025Article
- PemB, a type III secretion effector inHeliyon · 2024Article
- Reduced Bioactive Microbial Products (Pathogen-Associated Molecular Patterns) Contribute to Dysregulated Immune Responses and Impaired Healing in Infected Wounds in Mice with Diabetes.The Journal of investigative dermatology · 2024Article
- Review
- 14-3-3 Activated Bacterial Exotoxins AexT and ExoT Share Actin and the SH2 Domains of CRK Proteins as Targets for ADP-Ribosylation.Pathogens (Basel, Switzerland) · 2022Article
- Airway Epithelial Cell Junctions as Targets for Pathogens and Antimicrobial Therapy.Pharmaceutics · 2022Review
- Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics.Signal transduction and targeted therapy · 2022Review
- 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
- Presence of CrkI-containing microvesicles in squamous cell carcinomas could have ramifications on tumor biology and cancer therapeutics.Scientific reports · 2022Article
- CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT.Nature communications · 2022Article
- Article
- Therapeutic evaluation of immunomodulators in reducing surgical wound infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- What Makes Pseudomonas aeruginosa a Pathogen?Advances in experimental medicine and biology · 2022Article
- Therapeutic assessment of N-formyl-methionyl-leucyl-phenylalanine (fMLP) in reducing periprosthetic joint infection.European cells & materials · 2021Article
- Pseudomonas aeruginosa ExoT induces G1 cell cycle arrest in melanoma cells.Cellular microbiology · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Previously, we demonstrated that Pseudomonas aeruginosa ExoT induces potent apoptosis in host epithelial cells in a manner that primarily depends on its ADP-ribosyltransferase domain (ADPRT) activity. However, the mechanism underlying ExoT/ADPRT-induced apoptosis remains undetermined. We now report that ExoT/ADPRT disrupts focal adhesion sites, activates p38β and JNK, and interferes with integrin-mediated survival signaling; causing atypical anoikis. We show that ExoT/ADPRT-induced anoikis is mediated by the Crk adaptor protein. We found that Crk-/- knockout cells are significantly more resistant to ExoT-induced apoptosis, while Crk-/- cells complemented with Crk are rendered sensitive to ExoT-induced apoptosis. Moreover, a dominant negative (DN) mutant form of Crk phenocopies ExoT-induced apoptosis both kinetically and mechanistically. Crk is generally believed to be a component of focal adhesion (FA) and its role in cellular survival remains controversial in that it has been found to be either pro-survival or pro-apoptosis. Our data demonstrate that although Crk is recruited to FA sites, its function is likely not required for FA assembly or for survival per se. However, when modified by ExoT or by mutagenesis, it can be transformed into a cytotoxin that induces anoikis by disrupting FA sites and interfering with integrin survival signaling. To our knowledge, this is the first example whereby a bacterial toxin exerts its cytotoxicity by subverting the function of an innocuous host cellular protein and turning it against the host cell.
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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.