Regulatory mechanisms of thiol-based redox sensors: lessons learned from structural studies on prokaryotic redox sensors

Arch Pharm Res. 2018 Jun;41(6):583-593. doi: 10.1007/s12272-018-1036-0. Epub 2018 May 17.

Abstract

Oxidative stresses, such as reactive oxygen species, reactive electrophilic species, reactive nitrogen species, and reactive chlorine species, can damage cellular components, leading to cellular malfunction and death. In response to oxidative stress, bacteria have evolved redox-responsive sensors that enable them to simultaneously monitor and eradicate potential oxidative stress. Specifically, redox-sensing transcription regulators react to oxidative stress by means of modifying the thiol groups of cysteine residues, functioning as part of an efficient survival mechanism for many bacteria. In general, oxidative molecules can induce changes in the three-dimensional structures of redox sensors, which, in turn, affects the transcription of specific genes in detoxification pathways and defense mechanisms. Moreover, pathogenic bacteria utilize these redox sensors for adaptation and to evade subsequent oxidative attacks from host immune defense. For this reason, the redox sensors of pathogenic bacteria are potential antibiotic targets. Understanding the regulatory mechanisms of thiol-based redox sensors in bacteria will provide insight and knowledge into the discovery of new antibiotics.

Keywords: Bacteria; Protein structure; Redox sensor; Redox signaling; Transcription factor.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects
  • Bacteria / metabolism*
  • Bacterial Physiological Phenomena / drug effects
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Cysteine / chemistry
  • Drug Discovery
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / physiology*
  • Protein Structure, Tertiary / physiology
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Transcription Factors
  • Cysteine