ArticleRedox report : communications in free radical research2011
The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue.
Article in Redox report : communications in free radical research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- An insight into pyocyanin: production, characterization, and evaluation of its in vitro antibacterial, antifungal, antibiofilm and in vivo anti-schistosomal potency.BMC microbiology · 2025Article
- Fragment library screening by X-ray crystallography and binding site analysis on thioredoxin glutathione reductase of Schistosoma mansoni.Scientific reports · 2024Article
- The two faces of pyocyanin - why and how to steer its production?World journal of microbiology & biotechnology · 2023Review
- Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1Beilstein journal of organic chemistry · 2022Article
- Evaluation of Blood-Brain-Barrier Permeability, Neurotoxicity, and Potential Cognitive Impairment byOxidative medicine and cellular longevity · 2022Article
- Druggable hot spots in trypanothione reductase: novel insights and opportunities for drug discovery revealed by DRUGpy.Journal of computer-aided molecular design · 2021Article
- The Relevance of Glutathione Reductase Inhibition by Fluoxetine to Human Health and Disease: Insights Derived from a Combined Kinetic and Docking Study.The protein journal · 2019Article
- A high susceptibility to redox imbalance of the transmissible stages of Plasmodium falciparum revealed with a luciferase-based mature gametocyte assay.Molecular microbiology · 2017Article
- The Pyruvate and α-Ketoglutarate Dehydrogenase Complexes ofThe Journal of biological chemistry · 2017Article
- Antifungal Action of Methylene Blue Involves Mitochondrial Dysfunction and Disruption of Redox and Membrane Homeostasis in C. albicans.The open microbiology journal · 2016Article
- Mitochondrial Activity and Cyr1 Are Key Regulators of Ras1 Activation of C. albicans Virulence Pathways.PLoS pathogens · 2015Article
- The structural biology of phenazine biosynthesis.Current opinion in structural biology · 2014Review
- Analysis of Candida albicans mutants defective in the Cdk8 module of mediator reveal links between metabolism and biofilm formation.PLoS genetics · 2014Article
- CrowdPhase: crowdsourcing the phase problem.Acta crystallographica. Section D, Biological crystallography · 2014Article
- Thioredoxin reductase and its inhibitors.Current protein & peptide science · 2014Review
- Methylene blue for distributive shock: a potential new use of an old antidote.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2013Review
- Impact of methylene blue and atorvastatin combination therapy on the apparition of cerebral malaria in a murine model.Malaria journal · 2013Article
- Control of Candida albicans metabolism and biofilm formation by Pseudomonas aeruginosa phenazines.mBio · 2013Article
- Real-time imaging of the intracellular glutathione redox potential in the malaria parasite Plasmodium falciparum.PLoS pathogens · 2013Article
- 1,4-naphthoquinones and other NADPH-dependent glutathione reductase-catalyzed redox cyclers as antimalarial agents.Current pharmaceutical design · 2013Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The quorum sensor and signalling molecule pyocyanin (PYO) contributes significantly to the pathophysiology of Pseudomonas aeruginosa infections. Comparison to phenothiazine drugs suggests that the antimalarial compound methylene blue (MB) can be regarded as a sulfur analog of PYO. This working hypothesis would explain why the synthetic drug MB behaves as a compound shaped in biological evolution. Here we report on redox-associated biological and biochemical properties of PYO in direct comparison to its synthetic analog MB. We quantitatively describe the reactivity of both compounds toward cellular reductants, the reactivity of their reduced leuco-forms towards O2, and their interactions with FAD-containing disulfide reductases. Furthermore, the interaction of PYO with human glutathione reductase was studied in structural detail by x-ray crystallography, showing that a single PYO molecule binds to the intersubunit cavity of the enzyme. Like MB, also PYO was also found to be active against blood schizonts of the malaria parasite P. falciparum in vitro. Furthermore, both compounds were active against the disease transmitting gametocyte forms of the parasites, which was systematically studied in vitro. As shown for mice, PYO is too toxic to be used as a drug. It may, however, have antimalarial activity in numerous human patients with concomitant Pseudomonas infections. MB, in contrast to PYO, is well tolerated and represents a promising agent for MB-based combination therapies against malaria. Current and future clinical studies can be guided by the comparisons between MB and PYO reported here. Additionally, it is of interest to study if and to what extent the protection from malaria in patients with cystic fibrosis or with severe wound infections is based on PYO produced by Pseudomonas species.
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