<i>Staphylococcus Aureus</i> V8 protease disrupts the integrity of the airway epithelial barrier and impairs IL‐6 production in vitro

Murphy, Jae; Ramezanpour, Mahnaz; Stach, Natalia; Dubin, Grzegorz; Psaltis, Alkis J.; Wormald, Peter‐John; Vreugde, Sarah

doi:10.1002/lary.26949

Cited by 44 publications

(32 citation statements)

References 49 publications

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“…Tight junctions are involved in the regulation of solute and ion transport across epithelia and are localised at the apicolateral border of individual airway epithelial cells 3 , 5 , 60 . Certain bacterial 41 , 61 , 62 and viral 42 , 63 pathogens specifically target and degrade the tight junctions of airway epithelia during paracellular infection processes. Therefore, the presence of normal, functioning tight junctions is an essential feature of differentiated AECs to allow for representative modelling of respiratory tract infections.…”

Section: Discussionmentioning

confidence: 99%

Temporal differentiation of bovine airway epithelial cells grown at an air-liquid interface

Cozens

Sutherland

Marchesi

et al. 2018

Sci Rep

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There is an urgent need to develop improved, physiologically-relevant in vitro models of airway epithelia with which to better understand the pathological processes associated with infection, allergies and toxicological insults of the respiratory tract of both humans and domesticated animals. In the present study, we have characterised the proliferation and differentiation of primary bovine bronchial epithelial cells (BBECs) grown at an air-liquid interface (ALI) at three-day intervals over a period of 42 days from the introduction of the ALI. The differentiated BBEC model was highly representative of the ex vivo epithelium from which the epithelial cells were derived; a columnar, pseudostratified epithelium that was highly reflective of native airway epithelium was formed which comprised ciliated, goblet and basal cells. The hallmark defences of the respiratory tract, namely barrier function and mucociliary clearance, were present, thus demonstrating that the model is an excellent mimic of bovine respiratory epithelium. The epithelium was fully differentiated by day 21 post-ALI and, crucially, remained healthy and stable for a further 21 days. Thus, the differentiated BBEC model has a three-week window which will allow wide-ranging and long-term experiments to be performed in the fields of infection, toxicology or general airway physiology.

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Section: Discussionmentioning

confidence: 99%

Temporal differentiation of bovine airway epithelial cells grown at an air-liquid interface

Cozens

Sutherland

Marchesi

et al. 2018

Sci Rep

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“…SspA is produced upon S. aureus phagocytosis by neutrophils, suggesting its role in facilitating S. aureus intracellular escape, potentially through activating the cysteine protease, Staphopain B (254). SspA can disrupt epithelial barriers, compromising cell junction integrity (265,268). Skin infection models of sspA mutants suggest a slight decrease in bacterial fitness in vivo (269).…”

Section: B) Enzymes That Degrade Host Tissue Componentsmentioning

confidence: 99%

Staphylococcus aureusSecreted Toxins and Extracellular Enzymes

2019

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S. aureus is a formidable pathogen capable of causing infections in different sites of the body in a variety of vertebrate animals, including humans and livestock. A major contribution to the success of S. aureus as a pathogen is the plethora of virulence factors that manipulate the host's innate and adaptive immune responses. Many of these immune modulating virulence factors are secreted toxins, cofactors for activating host zymogens, and exoenzymes. Secreted toxins, such as poreforming toxins and superantigens are highly inflammatory and can cause leukocyte cell death by cytolysis and clonal deletion, respectively. Coagulases and staphylokinases are cofactors that hijack the host's coagulation system. Exoenzymes, including nucleases and proteases, cleave and inactivate various immune defense and surveillance molecules, such as complement factors, antimicrobial peptides, and surface receptors important for leukocyte chemotaxis. Additionally, some of these secreted toxins and exoenzymes can cause disruption of endothelial and epithelial barriers through cell lysis and cleavage of junction proteins. A unique feature when examining the repertoire of S. aureus secreted virulence factors is the apparent functional redundancy exhibited by the majority of the toxins and exoenzymes. However, closer examination of each virulence factor revealed that each has unique properties that have important functional consequences. This chapter will provide a brief overview of the current understanding on the major secreted virulence factors critical for S. aureus pathogenesis.

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“…It is frequently found in severe chronic inflammatory diseases of the gut, skin, and airway such as inflammatory bowel disease, allergic dermatitis, and asthma (Weidinger et al, 2008; Turner, 2009). In the context of CRS, bacterial secreted products as well as different cytokines have been reported to disrupt the mucosal barrier in vitro , and barrier dysfunction has been proposed to have a critical role in the pathogenesis of this disease (Tieu et al, 2009; Soyka et al, 2012; Malik et al, 2015; Ramezanpour et al, 2016; Murphy et al, 2017). Results of previous studies with primary alveolar pneumocytes indicated that P. aeruginosa elastase enhanced epithelial permeability by redistribution and disruption of tight junction proteins (Azghani et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosa Exoprotein-Induced Barrier Disruption Correlates With Elastase Activity and Marks Chronic Rhinosinusitis Severity

Ramezanpour

Fong

et al. 2019

Front. Cell. Infect. Microbiol.

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Background: Pseudomonas aeruginosa causes severe chronic respiratory diseases and is associated with recalcitrant chronic rhinosinusitis (CRS). P. aeruginosa exoproteins contain virulence factors and play important roles in the pathogenicity of P. aeruginosa , however their role in CRS pathophysiology remains unknown. Methods: We isolated P. aeruginosa clinical isolates (CIs) and obtained clinical information from 21 CRS patients. Elastase activity of the CIs was measured at different phases of growth. Primary human nasal epithelial cells (HNECs) were cultured at air-liquid interface (ALI) and challenged with P. aeruginosa exoproteins or purified elastase, followed by measuring Transepithelial Electrical Resistance (TEER), permeability of FITC-dextrans, western blot, and immunofluorescence. Results: 14/21 CIs had a significant increase in elastase activity in stationary phase of growth. There was a highly significant strong correlation between the in vitro elastase activity of P. aeruginosa CIs with mucosal barrier disruption evidenced by increased permeability of FITC-dextrans ( r = 0.95, p = 0.0004) and decreased TEER ( r = −0.9333, P < 0.01) after 4 h of challenge. Western blot showed a significant degradation of ZO-1, Occludin and β-actin in relation to the elastase activity of the exoproteins. There was a highly significant correlation between the in vitro elastase activity of P. aeruginosa CIs and CRS disease severity (for log phase, r = 0.5631, p = 0.0097; for stationary phase, r = 0.66, p = 0.0013) assessed by CT imaging of the paranasal sinuses. Conclusion: Our results implicate P. aeruginosa exoproteins as playing a major role in the pathophysiology of P. aeruginosa associated CRS by severely compromising mucosal barrier structure and function.

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Staphylococcus Aureus V8 protease disrupts the integrity of the airway epithelial barrier and impairs IL‐6 production in vitro

Cited by 44 publications

References 49 publications

Temporal differentiation of bovine airway epithelial cells grown at an air-liquid interface

Temporal differentiation of bovine airway epithelial cells grown at an air-liquid interface

Staphylococcus aureusSecreted Toxins and Extracellular Enzymes

Pseudomonas aeruginosa Exoprotein-Induced Barrier Disruption Correlates With Elastase Activity and Marks Chronic Rhinosinusitis Severity

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