Pseudomonas Aeruginosa Causes Endoplasmic Reticulum Stress In Primary Bronchial Epithelial Cells Which Is Associated With Disruption Of Tight Junctions

Wout, Emily F. A. van’t; Schadewijk, Annemarie van; Stolk, Jan; Hiemstra, Pieter S.

doi:10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a1068

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“…P. aeruginosa have been shown to invade airway epithelial barriers by destroying tight junctions (38), while Pseudomonas elastase can disrupt the tight junction in human nasal epithelial cells by downregulating the transmembrane proteins claudin-1 and-4, occludin, and tricellulin (39). ER stress induced by P. aeruginosa has also been implicated as a cause of tight junction destruction in primary bronchial epithelial cells (40). More recently, a strong correlation between in vitro elastase activity of clinical isolates of P. aeruginosa and mucosal barrier dysfunction has been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Impaired Airway Epithelial Barrier Integrity in Response to Stenotrophomonas maltophilia Proteases, Novel Insights Using Cystic Fibrosis Bronchial Epithelial Cell Secretomics

et al. 2020

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Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen that can chronically colonize the lungs of people with cystic fibrosis (CF) and is associated with lethal pulmonary hemorrhage in immunocompromised patients. Its secreted virulence factors include the extracellular serine proteases StmPR1, StmPR2, and StmPR3. To explore the impact of secreted virulence determinants on pulmonary mucosal defenses in CF, we examined the secretome of human CFBE41o-bronchial epithelial cells in response to treatment with S. maltophilia K279a cell culture supernatant (CS) using a liquid-chromatography-tandem mass spectrometry (LC-MS/MS) based label-free quantitative (LFQ) shotgun proteomics approach for global profiling of the cell secretome. Secretome analysis identified upregulated pathways mainly relating to biological adhesion and epithelial cell signaling in infection, whereas no specific pathways relating to the immune response were enriched. Further exploration of the potentially harmful effects of K279a CS on CF bronchial epithelial cells, demonstrated that K279a CS caused CFBE41o-cell condensation and detachment, reversible by the serine protease inhibitor PMSF. K279a CS also decreased trans-epithelial electrical resistance in CFBE41o-cell monolayers suggestive of disruption of tight junction complexes (TJC). This finding was corroborated by an observed increase in fluorescein isothiocyanate (FITC) dextran permeability and by demonstrating PMSF-sensitive degradation of the tight junction proteins ZO-1 and occludin, but not JAM-A or claudin-1. These observations demonstrating destruction of the CFBE41o-TJC provide a novel insight regarding the virulence of S. maltophilia and may explain the possible injurious effects of this bacterium on the CF bronchial epithelium and the pathogenic mechanism leading to lethal pulmonary hemorrhage.

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Section: Discussionmentioning

confidence: 99%