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Published on: June 21, 2021
Simultaneous Activation of Iron- and Thiol-Based Sensor-Regulator Systems by Redox-Active Compounds
Kang-Lok Lee1, Ji-Sun Yoo1, Gyeong-Seok Oh1
1School of Biological Sciences and Institute of Microbiology, Seoul National University Seoul, South Korea.
This study monitored multiple bacterial stress response pathways to reveal the diverse chemical activities of reactive compounds. This approach uncovers novel compound effects and provides a comprehensive understanding of cellular responses to oxidative and electrophilic stress.
Area of Science:
- Microbiology and Molecular Biology
- Biochemistry and Chemical Biology
Background:
- Bacteria encounter diverse redox-active compounds (RACs) in natural environments, including reactive oxygen species (ROS) and reactive electrophile species (RES).
- These compounds induce cellular stress by oxidizing or alkylating thiols, modulating sensitive regulators and activating response pathways.
- Previous studies often focused on single regulatory pathways, limiting the understanding of a compound's multifaceted effects.
Purpose of the Study:
- To investigate the comprehensive chemical activities of representative RACs in the model actinobacterium *Streptomyces coelicolor*.
- To develop and apply a method for time-course monitoring of multiple sensitive regulatory pathways to predict compound activities.
- To reveal novel pathways of cellular regulation by reactive compounds.
Main Methods:
- Monitoring the activity of three key sensor-regulators: SoxR (senses RACs via [2Fe-2S] cluster oxidation), CatR/PerR (senses peroxides via iron binding), and RsrA (senses RES via disulfide formation).
- Time-course analysis of target transcript induction for each regulator in response to various RACs.
- Utilizing *Streptomyces coelicolor* as the model organism.
Main Results:
- Phenazine methosulfate (PMS) was identified as an effective RAC and ROS producer.
- *p*-Benzoquinone showed potent RAC, ROS-producing, and RES activities, notably inducing the RsrA-SigR system via cysteine thiol adducts.
- Plumbagin, diamide, and monobromobimane exhibited varying degrees of RAC, ROS-producing, and RES activities, with diamide being a potent RES.
Conclusions:
- Monitoring multiple regulator responses provides a comprehensive profile of a compound's chemical activities *in vivo*.
- The study revealed novel mechanisms of RsrA regulation by benzoquinone, highlighting its sensitivity to electrophilic modification.
- This integrated approach offers a powerful tool for characterizing the complex interactions between chemicals and cellular regulatory networks.
Related Concept Videos
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Redox Reactions
Global Regulatory Systems
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Redox Titration: Other Oxidizing and Reducing Agents
Other Stress Responses in Bacteria

