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Quercetin Caused Redox Homeostasis Imbalance and Activated the Kynurenine Pathway (Running Title: Quercetin Caused Oxidative Stress).

ABSTRACT: The search for new and better antimicrobial therapy is a continuous effort. Quercetin is a polyphenol with promising antimicrobial properties. However, the understanding of its antimicrobial mechanism is limited. In this study, we investigated the biochemical mechanistic action of quercetin as an antibacterial compound. Isolates of Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, and Staphylococcus aureus were initially exposed to quercetin for antibacterial evaluation. Subsequently, S. aureus (Gram-positive) and E. coli (Gram-negative) cells were exposed to quercetin with or without ascorbic acid, and cells were harvested for selected biochemical assays. These assays included redox homeostasis (lipid peroxidation, total thiol, total antioxidant capacity), nitric oxide, and kynurenine concentration as well as DNA fragmentation. The results revealed that quercetin caused lipid peroxidation in the bacterial isolates. Lipid peroxidation may indicate ensuing oxidative stress resulting from quercetin treatment. Furthermore, tryptophan degradation to kynurenine was activated by quercetin in S. aureus but not in E. coli, suggesting that local L-tryptophan concentration might become limiting for bacterial growth. These findings, considered together, may indicate that quercetin restricts bacterial growth by promoting oxidative cellular stress, as well as by reducing the local L-tryptophan availability by activating the kynurenine pathway, thus contributing to our understanding of the molecular mechanism of the antimicrobial action of quercetin.

SUBMITTER: Adeyemi OS

PROVIDER: S-EPMC7465034 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Quercetin Caused Redox Homeostasis Imbalance and Activated the Kynurenine Pathway (Running Title: Quercetin Caused Oxidative Stress).

Adeyemi Oluyomi Stephen OS Ebugosi Chinemerem C Akpor Oghenerobor Benjamin OB Hetta Helal F HF Al-Rashed Sarah S Otohinoyi David Adeiza DA Rotimi Damilare D Owolabi Akinyomade A Evbuomwan Ikponmwosa Owen IO Batiha Gaber El-Saber GE

Biology 20200810 8

The search for new and better antimicrobial therapy is a continuous effort. Quercetin is a polyphenol with promising antimicrobial properties. However, the understanding of its antimicrobial mechanism is limited. In this study, we investigated the biochemical mechanistic action of quercetin as an antibacterial compound. Isolates of <i>Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia,</i> and <i>Staphylococcus aureus</i> were initially exposed to quercetin for ant ...[more]

PMID: 32785180

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Project description:The AdhR regulatory protein is an activator of σ54-dependent transcription of adhA1 and adhA2 genes, which are required for alcohol synthesis in Clostridium beijerinckii Here, we identified the signal perceived by AdhR and determined the regulatory mechanism of AdhR activity. By assaying the activity of AdhR in N-terminally truncated forms, a negative control mechanism of AdhR activity was identified in which the central AAA+ domain is subject to repression by the N-terminal GAF and PAS domains. Binding of Fe2+ to the GAF domain was found to relieve intramolecular repression and stimulate the ATPase activity of AdhR, allowing the AdhR to activate transcription. This control mechanism enables AdhR to regulate transcription of adhA1 and adhA2 in response to cellular redox status. The mutants deficient in AdhR or σ54 showed large shifts in intracellular redox state indicated by the NADH/NAD+ ratio under conditions of increased electron availability or oxidative stress. We demonstrated that the Fe2+-activated transcriptional regulator AdhR and σ54 control alcohol synthesis to maintain redox homeostasis in clostridial cells. Expression of N-terminally truncated forms of AdhR resulted in improved solvent production by C. beijerinckiiIMPORTANCE Solventogenic clostridia are anaerobic bacteria that can produce butanol, ethanol, and acetone, which can be used as biofuels or building block chemicals. Here, we show that AdhR, a σ54-dependent transcriptional activator, senses the intracellular redox status and controls alcohol synthesis in Clostridium beijerinckii AdhR provides a new example of a GAF domain coordinating a mononuclear non-heme iron to sense and transduce the redox signal. Our study reveals a previously unrecognized functional role of σ54 in control of cellular redox balance and provides new insights into redox signaling and regulation in clostridia. Our results reveal AdhR as a novel engineering target for improving solvent production by C. beijerinckii and other solventogenic clostridia.

Dataset Information

Quercetin Caused Redox Homeostasis Imbalance and Activated the Kynurenine Pathway (Running Title: Quercetin Caused Oxidative Stress).

Publications

Quercetin Caused Redox Homeostasis Imbalance and Activated the Kynurenine Pathway (Running Title: Quercetin Caused Oxidative Stress).

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