Effect of Pseudomonas aeruginosa-derived pyocyanin and 1-hydroxyphenazine on pulmonary mucociliary clearance monitored scintigraphically in the baboon model

Dormehl, I. C.; Ras, G J; Taylor, Graham W.; Hugo, N.

doi:10.1016/0883-2897(91)90105-t

Cited by 15 publications

(7 citation statements)

References 11 publications

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“…Pyocyanin has been recovered from CF and non-CF bronchiectatic airways at 0.1 mM concentrations [ 193 , 194 ]. Earlier studies have shown that pyocyanin damages ciliated epithelium, interferes with ciliary function, inhibits mucous transport [ 193 ], induces neutrophilia and bronchoconstriction in sheep airways [ 195 , 196 ], and decreases mucus velocity in trachea [ 197 , 198 ]. Additionally, the levels of pyocyanin negatively correlate with the lung function of CF patients [ 194 ].…”

Section: Exoproducts and Secretion Systemsmentioning

confidence: 99%

An Organ System-Based Synopsis ofPseudomonas aeruginosaVirulence

et al. 2021

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Driven in part by its metabolic versatility, high intrinsic antibiotic resistance, and a large repertoire of virulence factors, Pseudomonas aeruginosa is expertly adapted to thrive in a wide variety of environments, and in the process, making it a notorious opportunistic pathogen. Apart from the extensively studied chronic infection in the lungs of people with cystic fibrosis (CF), P. aeruginosa also causes multiple serious infections encompassing essentially all organs of the human body, among others, lung infection in patients with chronic obstructive pulmonary disease, primary ciliary dyskinesia and ventilator-associated pneumonia; bacteremia and sepsis; soft tissue infection in burns, open wounds and postsurgery patients; urinary tract infection; diabetic foot ulcers; chronic suppurative otitis media and otitis externa; and keratitis associated with extended contact lens use. Although well characterized in the context of CF, pathogenic processes mediated by various P. aeruginosa virulence factors in other organ systems remain poorly understood. In this review, we use an organ system-based approach to provide a synopsis of disease mechanisms exerted by P. aeruginosa virulence determinants that contribute to its success as a versatile pathogen.

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Section: Exoproducts and Secretion Systemsmentioning

confidence: 99%

An Organ System-Based Synopsis ofPseudomonas aeruginosaVirulence

et al. 2021

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“…Additionally, the levels of pyocyanin within sputa negatively-correlates with the function of CF lungs (82). Pyocyanin interferes with ciliary beating and mucus transport (81), induces bronchoconstriction (83), and decreases mucus velocity (84,85). Mouse lungs chronically-exposed to pyocyanin develop goblet cell hyperplasia and metaplasia, peribronchial fibrosis, and alveolar airspace destruction, accompanied by polarization from initially a Th1 response toward a Th2 response dominated by IL-4 and IL-13 secreted by activated macrophages and CD4 + T cells, with concomitant influx of neutrophils (52,66).…”

Section: Foxa2 Inactivation By Respiratory Bacterial Pathogensmentioning

confidence: 99%

Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis

2020

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Forkhead box (FOX) proteins are transcriptional factors that regulate various cellular processes. This minireview provides an overview of FOXA2 functions, with a special emphasis on the regulation airway mucus homeostasis in both healthy and diseased lungs. FOXA2 plays crucial roles during lung morphogenesis, surfactant protein production, goblet cell differentiation and mucin expression. In healthy airways, FOXA2 exerts a tight control over goblet cell development and mucin biosynthesis. However, in diseased airways, microbial infections and proinflammatory responses deplete FOXA2 expression, resulting in uncontrolled goblet cell hyperplasia and metaplasia, mucus hypersecretion, and impaired mucociliary clearance of pathogens. Furthermore, accumulated mucus clogs the airways and creates a niche environment for persistent microbial colonization and infection, leading to acute exacerbation and deterioration of pulmonary function in patients with chronic lung diseases. Various studies have shown that FOXA2 inhibition is mediated through induction of antagonistic EGFR and IL-13R-STAT6 signaling pathways as well as through posttranslational modifications induced by microbial infections. An improved understanding of how bacterial pathogens inactivate FOXA2 may pave the way for developing therapeutics that preserve the protein's function, which in turn, will improve the mucus status and mucociliary clearance of pathogens, reduce microbial-mediated acute exacerbation and restore lung function in patients with chronic lung diseases.

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“…It has a number of deleterious effects on eukaryotic cells, including epithelial cells, endothelial cells, and leukocytes (20,28,32,33,42,45,46,52,59,65). These include reversible ciliary dysfunction in human respiratory and sheep tracheal epithelial cells (1,28,33,70,71), bronchoconstriction and neutrophilia in sheep (18,37), and a decrease in in vivo tracheal mucus velocity in several animal models (13,47,56). In vitro, pyocyanin inhibits neutrophil, monocyte, and lymphocyte microbicidal functions (42-46, 48, 59, 60); enhances neutrophil inactivation of ␣ 1 -protease inhibitor (53); inhibits endothelial cell and macrophage nitric oxide production (23,27,57,68); blocks endothelial cell prostacyclin production (32); and promotes apoptosis in neutrophils (66).…”

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confidence: 99%

ThePseudomonassecretory product pyocyanin inhibits catalase activity in human lung epithelial cells

O’Malley¹,

Reszka²,

Rasmussen³

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pyocyanin, produced by Pseudomonas aeruginosa, has many deleterious effects on human cells that relate to its ability to generate reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Human cells possess several mechanisms to protect themselves from ROS, including manganese superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and catalase. Given the link between pyocyanin-mediated epithelial cell injury and oxidative stress, we assessed pyocyanin's effect on MnSOD, CuZnSOD, and catalase levels in the A549 human alveolar epithelial cell line and in normal human bronchial epithelial cells. In both cell types, CuZnSOD and MnSOD were unaltered, but over 24 h pyocyanin significantly decreased cellular catalase activity and protein content. Pyocyanin also decreased catalase mRNA. Overexpression of MnSOD in A549 cells prevented pyocyanin-mediated loss of catalase protein, but catalase activity still declined. Furthermore, pyocyanin decreased catalase activity, but not protein, in A549 cells overexpressing human catalase. These data suggest a direct effect of pyocyanin on catalase activity. Addition of pyocyanin to catalase in a cell-free system also decreased catalase activity. Mammalian catalase binds four NADPH molecules, helping maintain enzyme activity. Spin-trapping data suggest that pyocyanin directly oxidizes this NADPH, producing superoxide. We conclude that pyocyanin may decrease cellular catalase activity via both transcriptional regulation and direct inactivation of the enzyme. Decreased cellular catalase activity and failure to augment MnSOD could contribute to pyocyanin-dependent cytotoxicity.

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Effect of Pseudomonas aeruginosa-derived pyocyanin and 1-hydroxyphenazine on pulmonary mucociliary clearance monitored scintigraphically in the baboon model

Cited by 15 publications

References 11 publications

An Organ System-Based Synopsis ofPseudomonas aeruginosaVirulence

An Organ System-Based Synopsis ofPseudomonas aeruginosaVirulence

Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis

ThePseudomonassecretory product pyocyanin inhibits catalase activity in human lung epithelial cells

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