Disease relevance of PYOCYANINE

• Pyocyanin, a secretory product of Pseudomonas aeruginosa, has the capacity to undergo redox cycling under aerobic conditions with resulting generation of superoxide and hydrogen peroxide [1].
• Pseudomonas aeruginosa produces copious amounts of the redoxactive tricyclic compound pyocyanin that kills competing microbes and mammalian cells, especially during cystic fibrosis lung infection [2].
• Cyanide-insensitive respiration, used as an indicator of intracellular superoxide and/or hydrogen peroxide production, was 50-fold less in pyocyanin-treated P. aeruginosa than in E. coli [3].
• The Pseudomonas aeruginosa secretory product pyocyanin inactivates alpha1 protease inhibitor: implications for the pathogenesis of cystic fibrosis lung disease [4].
• Subcellular site(s) of pyocyanin redox cycling and toxicity have not been well studied [5].

Psychiatry related information on PYOCYANINE

• From these results we conclude that this property of pyocyanine may lead to suppression of specific defense mechanisms and enhance harmful inflammatory reactions of the host during infection with Pseudomonas aeruginosa [6].

High impact information on PYOCYANINE

• Similarly, endothelial cell exposure to pyocyanin and ferripyochelin also resulted in hydroxyl radical production which appeared to occur in close proximity to the cell surface [1].
• The antibiotic properties of pyocyanin, produced by Pseudomonas aeruginosa, were recognized in the 1890s, although this blue phenazine is now known to be a virulence factor in human disease [7].
• Using cultured human lung epithelial cells, we showed that pyocyanin-mediated reactive oxygen intermediates inactivate human vacuolar ATPase, supporting the validity of the yeast screen [2].
• Pyocyanin production by Pseudomonas aeruginosa induces neutrophil apoptosis and impairs neutrophil-mediated host defenses in vivo [8].
• Among recognized virulence factors is the redox-active phenazine pyocyanin [9].

Chemical compound and disease context of PYOCYANINE

• These data suggest the possibility that the P. aeruginosa secretory products pyocyanin and pyochelin may act synergistically via the generation of hydroxyl radical to damage local tissues at sites of pseudomonas infection [1].
• Cell extracts from E. coli contained an NADPH:pyocyanin oxidoreductase which increased the rate of reduction of pyocyanin by NADPH [3].
• The effects of the Pseudomonas aeruginosa-derived pigments, pyocyanin and 1-hydroxyphenazine (1-hp), on membrane-associated oxidative metabolism and release of lysozomal enzymes by human neutrophils were investigated in vitro [10].
• These data suggest that pyocyanin could contribute to lung injury in the P. aeruginosa-infected airway of cystic fibrosis patients by decreasing the ability of alpha1PI to control the local activity of serine proteases [4].
• The ability of unstimulated human PMNL to metabolize exogenous LTB4 was found to be inhibited by pyocyanin, a phenazine derivative produced by Pseudomonas aeruginosa, in a dose-dependent manner [11].

Biological context of PYOCYANINE

• Pyocyanin-induced apoptosis was associated with rapid and sustained generation of reactive oxygen intermediates and subsequent reduction of intracellular cAMP [12].
• Evidence is provided to show that the mexEF-oprN operon may be involved in the excretion of intermediates for the biosynthesis of pyocyanin, a typical secondary metabolite of P. aeruginosa [13].
• Through mutational analysis, we show that pyocyanin is the physiological signal for the upregulation of these quorum sensing-controlled genes during stationary phase and that the response is mediated by the transcription factor SoxR [14].
• In parallel, the gacA gene dosage markedly influenced the BHL/RhIR-dependent formation of the cytotoxic compounds pyocyanin and cyanide and the exoenzyme lipase [15].
• All cells treated with pyocyanin (10 muM) converted to the senescent phenotype, which remained stable for up to 7 days [16].

Anatomical context of PYOCYANINE

• As assessed by 51Cr release, endothelial cells which were treated with pyocyanin or ferripyochelin alone demonstrated minimal injury [1].
• In clinical isolates of P. aeruginosa pyocyanin production was associated with a proapoptotic effect upon neutrophils in culture [12].
• To determine the mechanism of the inhibitory action of pyocyanine, we studied its effect on the early stages of T cell activation [17].
• Pyocyanin induced a concentration- and time-dependent acceleration of neutrophil apoptosis, with 50 microM pyocyanin causing a 10-fold induction of apoptosis at 5 h (p < 0.001), a concentration that has been documented in sputum from patients colonized with P. aeruginosa [12].
• At a pyocyanine concentration of 0.1 micrograms/ml or less the proliferation of T and B lymphocytes was enhanced, but at 0.5 micrograms/ml it was suppressed [6].

Associations of PYOCYANINE with other chemical compounds

• We investigated the effects of two phenazines, pyocyanin and 1-hydroxyphenazine, upon apoptosis of neutrophils in vitro [12].
• We also showed that pyocyanine did not interfere with the function of calmodulin stimulated Ca2+-Mg2+ ATPase activity, indicating that the mechanism of action of pyocyanine differs from that of the structurally related phenothiazine compounds [17].
• Intracellular levels of NADPH increased up to 2.4-fold in response to pyocyanin exposure [18].
• However, since pyocyanin directly accepts electrons from NAD(P)H, we hypothesized that pyocyanin might directly oxidize DCFH2 to DCF without an ROS intermediate [19].
• Sources for O2-. and H2O2 included phorbol myristate acetate (PMA)-stimulated neutrophils and pyocyanin [20].

Gene context of PYOCYANINE

• In contrast to pgp-3 mutants, nhr-8 mutants are not more sensitive than wild-type to pyocyanin-dependent killing by the pathogenic bacterium Pseudomonas aeruginosa [21].
• These results suggest that PtxR negatively regulates the expression of the rhamnolipid and pyocyanin genes through rhlI and the pqsABCDE operon while it positively regulates the expression of lasB through lasI [22].
• In contrast to the dual effects of pyocyanine on lymphocyte response, lipopolysaccharide-induced IL-1 and tumor necrosis factor release by monocytes was markedly enhanced by low as well as high concentrations of pyocyanine [6].
• MvaT was identified as a novel global regulator of virulence gene expression, as a mutation in mvaT resulted in enhanced lecA expression and pyocyanin production [23].
• Introduction of an inactivated trpE gene into a phnA mutant abolished residual pyocyanin production, suggesting that the trpE trpG gene products are capable of providing some anthranilate for pyocyanin synthesis [24].
• Pharmacological inhibitors of a lysosomal protease, cathepsin D (CTSD), abrogated pyocyanin-induced apoptosis, and translocation of CTSD to the cytosol followed pyocyanin treatment and lysosomal disruption [25].

Analytical, diagnostic and therapeutic context of PYOCYANINE

• By using spin trapping techniques in conjunction with electron paramagnetic resonance spectrometry (EPR), superoxide was detected during the aerobic reduction of pyocyanin by NADH or porcine endothelial cells [1].
• Antioxidant intervention studies indicated both similarities and differences between PCA and pyocyanin [9].
• Pyocyanine was isolated by chloroform extraction of cultures of Pseudomonas aeruginosa, and purified by thin layer chromatography [26].
• However, T blasts generated by Con A in the presence of pyocyanine did not grow in response to IL2 even in the absence of pyocyanine, and IL2 receptors, detected by indirect immunofluorescence with the receptor-specific monoclonal antibody AMT-13, were diminished in pyocyanine-treated cells [26].
• Confocal and electron microscopy studies suggested mitochondrial redox cycling of pyocyanin and extracellular H(2)O(2) release, respectively [5].

References