Mechanism for glutathione-mediated protection against the Pseudomonas aeruginosa redox toxin, pyocyanin

Chemico-biological Interactions
Michael Muller, Neil D Merrett

Abstract

Pseudomonas aeruginosa is an important human pathogen associated with several acute and chronic conditions, including diseases of the airways and wounds. The organism produces pyocyanin, an extracellular redox toxin that induces oxidative stress, depletes intracellular glutathione (GSH) and induces proliferative arrest and apoptosis, thus compromising the ability of tissue to repair itself. GSH is an important intra- and extracellular antioxidant, redox buffer and detoxifies xenobiotics by increasing their polarity, which facilitates their elimination. As previous studies have reported exogenous GSH to be protective against pyocyanin toxicity, this study was undertaken to explore the mechanism by which GSH protects host cells from the deleterious effects of the toxin. Co-incubation of pyocyanin with GSH resulted in a time-dependent diminished recovery of the toxin from the incubation medium. Concurrently, a highly polar green-colored metabolite was recovered that exhibited a UV-visible spectrum similar to pyocyanin and which was determined by mass spectrometry to have a major ion (m/z = 516) consistent with a glutathione conjugate. The ability of the conjugate to oxidize NADPH and to reduce molecular oxygen with the production ...Continue Reading

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Citations

Jun 17, 2015·Chemico-biological Interactions·Rajkumar Cheluvappa, Rajaraman Eri
Jun 10, 2015·Chemico-biological Interactions·Michael Muller, Neil D Merrett
Sep 11, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Valeri V MossineThomas P Mawhinney
Jan 18, 2017·Bioorganic & Medicinal Chemistry·Nikolaus GuttenbergerRolf Breinbauer
May 23, 2018·Antimicrobial Agents and Chemotherapy·Valeri V MossineThomas P Mawhinney
May 16, 2018·Antimicrobial Agents and Chemotherapy·Michael Muller
Apr 29, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Qianru MaYufen Zhao
Jun 6, 2021·International Journal of Pharmaceutics·Li DingZhengrong Cui

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