Phenazine-1-carboxylic acid, a secondary metabolite of<i>Pseudomonas aeruginosa</i>, alters expression of immunomodulatory proteins by human airway epithelial cells

Denning, Gerene M.; Reszka, Krzysztof J.; O’Malley, Yunxia; Rasmussen, George T.; Britigan, Bradley E.

doi:10.1152/ajplung.00086.2003

Cited by 59 publications

(41 citation statements)

References 27 publications

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“…It is a blue compound that can oxidize or reduce other molecules present in the infection zone [38]. Pyocyanin is recognized as a virulence factor of P. aeruginosa strains that have strong cytotoxicity [39]. Amount of pyocyanin in P. aeruginosa was diminished, by 20% in tested mutant strain especially at 42…”

Section: Discussionmentioning

confidence: 99%

Effects of Null Mutation of the Heat-Shock Gene htpG on the Production of Virulence Factors by Pseudomonas Aeruginosa

2017

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Aim:Pseudomonas aeruginosa is one of the most clinically important opportunistic pathogen in humans. The aim of the project was to study effects of HtpG on the selected virulence factors responsible for pathogenesis and biofilm formation of P. aeruginosa. Methodology: By characterizing a htpG null mutant of P. aeruginosa, we have identified the role of HtpG in the production of selected factors. Results: We showed that htpG mutant affects many physiological processes containing: decreased activity of the LasA protease, reduction of biofilm formation, decreased motility, and diminished amount of rhamnolipids and pyoverdine/pyocyanin. These defects were most evident when the htpG strain was cultured at 42• C. Conclusion: Our findings demonstrate the unexplored role of HtpG in the pathogenicity of P. aeruginosa, and indicate potential targets for antibacterial therapeutics.

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Section: Discussionmentioning

confidence: 99%

Effects of Null Mutation of the Heat-Shock Gene htpG on the Production of Virulence Factors by Pseudomonas Aeruginosa

2017

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“…Studies from our laboratory demonstrate that both laboratory and clinical strains of the bacterium also secrete phenazine-1-carboxylic acid (PCA), the precursor for pyocyanin, and that PCA increases oxidant production, IL-8 release, and ICAM-1 expression by human airway epithelial cells (20). Moreover, like pyocyanin, PCA inhibits cytokine-dependent expression of RANTES and MCP-1.…”

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confidence: 96%

Pyocyanin and Its Precursor Phenazine-1-Carboxylic Acid Increase IL-8 and Intercellular Adhesion Molecule-1 Expression in Human Airway Epithelial Cells by Oxidant-Dependent Mechanisms

Look¹,

Stoll²,

Romig³

et al. 2005

The Journal of Immunology

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Pseudomonas aeruginosa secretes numerous factors that alter host cell function and may contribute to disease pathogenesis. Among recognized virulence factors is the redox-active phenazine pyocyanin. We have recently demonstrated that the precursor for pyocyanin, phenazine-1-carboxylic acid (PCA), increases oxidant formation and alters gene expression in human airway epithelial cells. We report in this work that PCA and pyocyanin increase expression of ICAM-1 both in vivo and in vitro. Moreover, phenazines enhanced cytokine-dependent increases in IL-8 and ICAM-1. Antioxidant intervention studies indicated both similarities and differences between PCA and pyocyanin. The thiol antioxidant N-acetyl cysteine, extracellular catalase, and inducible NO synthase inhibitors inhibited ICAM-1 and IL-8 increases in response to both phenazines. However, pyocyanin was significantly more sensitive to N-acetylcysteine inhibition. Interestingly, hydroxyl radical scavengers inhibited the response to pyocyanin, but not to PCA. These studies suggest that P. aeruginosa phenazines coordinately up-regulate chemokines (IL-8) and adhesion molecules (ICAM-1) by mechanisms that are, at least in part, oxidant dependent. However, results indicate that the mechanisms by which PCA and pyocyanin exert their effects are not identical, and not all antioxidant interventions are equally effective in inhibiting phenazine-mediated proinflammatory effects.

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“…Phenazines affect microbial communities in both positive and negative ways, and their presence correlates with decreased species richness and diversity (7). Phenazine-1-carboxylic acid is a biologically active factor that has several activities that could alter the host's immune and inflammatory response and thereby contribute to bacterial pathogenesis (8). However, the degradation characteristics of phenazine-1-carboxylic acid and the environmental consequences of the long-term application have not been clarified.…”

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confidence: 99%

Novel Three-Component Phenazine-1-Carboxylic Acid 1,2-Dioxygenase in Sphingomonas wittichii DP58

Zhao

Wang

et al. 2017

Appl Environ Microbiol

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Phenazine-1-carboxylic acid, the main component of shenqinmycin, is widely used in southern China for the prevention of rice sheath blight. However, the fate of phenazine-1-carboxylic acid in soil remains uncertain. Sphingomonas wittichii DP58 can use phenazine-1-carboxylic acid as its sole carbon and nitrogen sources for growth. In this study, dioxygenase-encoding genes, pcaA1A2, were found using transcriptome analysis to be highly upregulated upon phenazine-1-carboxylic acid biodegradation. PcaA1 shares 68% amino acid sequence identity with the large oxygenase subunit of anthranilate 1,2-dioxygenase from Rhodococcus maanshanensis DSM 44675. The dioxygenase was coexpressed in Escherichia coli with its adjacent reductase-encoding gene, pcaA3, and ferredoxin-encoding gene, pcaA4, and showed phenazine-1-carboxylic acid consumption. The dioxygenase-, ferredoxin-, and reductaseencoding genes were expressed in Pseudomonas putida KT2440 or E. coli BL21, and the three recombinant proteins were purified. A phenazine-1-carboxylic acid conversion capability occurred in vitro only when all three components were present. However, P. putida KT2440 transformed with pcaA1A2 obtained phenazine-1-carboxylic acid degradation ability, suggesting that phenazine-1-carboxylic acid 1,2-dioxygenase has low specificities for its ferredoxin and reductase. This was verified by replacing PcaA3 with RedA2 in the in vitro enzyme assay. High-performance liquid chromatography-mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR) analysis showed that phenazine-1-carboxylic acid was converted to 1,2-dihydroxyphenazine through decarboxylation and hydroxylation, indicating that PcaA1A2A3A4 constitutes the initial phenazine-1-carboxylic acid 1,2-dioxygenase. This study fills a gap in our understanding of the biodegradation of phenazine-1-carboxylic acid and illustrates a new dioxygenase for decarboxylation.IMPORTANCE Phenazine-1-carboxylic acid is widely used in southern China as a key fungicide to prevent rice sheath blight. However, the degradation characteristics of phenazine-1-carboxylic acid and the environmental consequences of the long-term application are not clear. S. wittichii DP58 can use phenazine-1-carboxylic acid as its sole carbon and nitrogen sources. In this study, a three-component dioxygenase, PcaA1A2A3A4, was determined to be the initial dioxygenase for phenazine-1-carboxylic acid degradation in S. wittichii DP58. Phenazine-1-carboxylic acid was converted to 1,2-dihydroxyphenazine through decarboxylation and hydroxylation. This finding may help us discover the pathway for phenazine-1-carboxylic acid degradation.KEYWORDS phenazine-1-carboxylic acid, S. wittichii DP58, biodegradation, dioxygenase P henazine-1-carboxylic acid, a type of phenazine compound produced by some Pseudomonas species, has strong suppressive activity toward various plant fungal pathogens, nematodes, and Gram-negative bacteria (1-4). The biocide shenqinmycin,

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Phenazine-1-carboxylic acid, a secondary metabolite ofPseudomonas aeruginosa, alters expression of immunomodulatory proteins by human airway epithelial cells

Abstract: . Phenazine-1-carboxylic acid, a secondary metabolite of Pseudomonas aeruginosa, alters expression of immunomodulatory proteins by human airway epithelial cells.

Cited by 59 publications

References 27 publications

Effects of Null Mutation of the Heat-Shock Gene htpG on the Production of Virulence Factors by Pseudomonas Aeruginosa

Effects of Null Mutation of the Heat-Shock Gene htpG on the Production of Virulence Factors by Pseudomonas Aeruginosa

Pyocyanin and Its Precursor Phenazine-1-Carboxylic Acid Increase IL-8 and Intercellular Adhesion Molecule-1 Expression in Human Airway Epithelial Cells by Oxidant-Dependent Mechanisms

Novel Three-Component Phenazine-1-Carboxylic Acid 1,2-Dioxygenase in Sphingomonas wittichii DP58

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