ArticlePLoS pathogens2015
Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells.
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 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- The cGAS-STING signaling pathway in the regulation of pulmonary infections: a systematic review.Frontiers in cellular and infection microbiology · 2025Pooled it
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- GRP78 dysregulation: A proposed molecular mechanism linking the tumor microenvironment to sepsis susceptibility in patients with cancer (Review).International journal of molecular medicine · 2026Review
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- Bacterial infection elicits theOpen biology · 2025Article
- Activation of the endoplasmic reticulum stress regulator IRE1α compromises pulmonary host defenses.Cell reports · 2025Article
- Modulation of pulmonary immune functions by theFrontiers in immunology · 2025Review
- Review
- The protective effects and mechanisms of rosmarinic acid againstFrontiers in pharmacology · 2025Article
- Modeling Host-Pathogen Interactions inInternational journal of molecular sciences · 2024Review
- Pyrrole-based inhibitors of RND-type efflux pumps reverse antibiotic resistance and display anti-virulence potential.PLoS pathogens · 2024Article
- Biofilm Formation, Pyocyanin Production, and Antibiotic Resistance Profile ofInternational journal of microbiology · 2024Article
- Chemical Chaperone 4-PBA Mitigates Tumor Necrosis Factor Alpha-Induced Endoplasmic Reticulum Stress in Human Airway Smooth Muscle.International journal of molecular sciences · 2023Article
- AMPK activation improves recovery from pneumonia-induced lung injury via reduction of er-stress and apoptosis in alveolar epithelial cells.Respiratory research · 2023Article
- Dysregulation of Stress-Induced Translational Control byMicroorganisms · 2023Article
- Cigarette smoke restricts the ability of mesenchymal cells to support lung epithelial organoid formation.Frontiers in cell and developmental biology · 2023Article
- Stress granules: potential therapeutic targets for infectious and inflammatory diseases.Frontiers in immunology · 2023Review
- Ivacaftor restores delayed mucociliary transport caused by Pseudomonas aeruginosa-induced acquired cystic fibrosis transmembrane conductance regulator dysfunction in rabbit nasal epithelia.International forum of allergy & rhinology · 2022Article
- Article
- Engineered Cell Line Imaging Assay Differentiates Pathogenic from Non-Pathogenic Bacteria.Pathogens (Basel, Switzerland) · 2022Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA). Efficient functioning of the endoplasmic reticulum (ER) is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded protein response" (UPR). Bacterial infection and Toll-like receptor activation trigger the UPR most likely due to the increased demand for protein folding of inflammatory mediators. In this study, we show that cell-free conditioned medium of the PAO1 strain of P. aeruginosa, containing secreted virulence factors, induces ER stress in primary bronchial epithelial cells as evidenced by splicing of XBP1 mRNA and induction of CHOP, GRP78 and GADD34 expression. Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA. Using various mutant strains and purified virulence factors, we identified pyocyanin and AprA as inducers of ER stress. However, the induction of GADD34 was mediated by an ER stress-independent integrated stress response (ISR) which was at least partly dependent on the iron-sensing eIF2α kinase HRI. Our data strongly suggest that this increased GADD34 expression served to protect against Pseudomonas-induced, iron-sensitive cell cytotoxicity. In summary, virulence factors from P. aeruginosa induce ER stress in airway epithelial cells and also trigger the ISR to improve cell survival of the host.
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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.