Virulence Factors of Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells
Pseudomonas aeruginosa causes a devastating infection when it affects patients with cystic fibrosis or other chronic lung diseases. It often causes chronic infection due to its resistance to antibiotic treatment and its ability to form biofilms in these patients. The toxic effects of P. aeruginosa are largely mediated by secreted virulence factors. Efficient functioning of the endoplasmic reticulum is crucial for cell survival and appropriate immune responses, while its dysfunction causes stress and activation of the unfolded protein response. In this study, we found that virulence factors secreted by P. aeruginosa trigger the unfolded protein response in human cells by causing endoplasmic reticulum stress. In addition, secreted virulence factors activate the integrated stress response via a parallel independent pathway. Both stress pathways lead to the induction of the protein GADD34, which appears to provide protection against the toxic effects of the secreted virulence factors.
Vyšlo v časopise:
Virulence Factors of Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004946
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004946
Souhrn
Pseudomonas aeruginosa causes a devastating infection when it affects patients with cystic fibrosis or other chronic lung diseases. It often causes chronic infection due to its resistance to antibiotic treatment and its ability to form biofilms in these patients. The toxic effects of P. aeruginosa are largely mediated by secreted virulence factors. Efficient functioning of the endoplasmic reticulum is crucial for cell survival and appropriate immune responses, while its dysfunction causes stress and activation of the unfolded protein response. In this study, we found that virulence factors secreted by P. aeruginosa trigger the unfolded protein response in human cells by causing endoplasmic reticulum stress. In addition, secreted virulence factors activate the integrated stress response via a parallel independent pathway. Both stress pathways lead to the induction of the protein GADD34, which appears to provide protection against the toxic effects of the secreted virulence factors.
Zdroje
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