Redox Impact on Bacterial Macromolecule: A Promising Avenue for Discovery and Development of Novel Antibacterials

Biomolecules. 2022 Oct 22;12(11):1545. doi: 10.3390/biom12111545.

Abstract

Antibiotic resistance in bacteria has remained a serious public health concern, resulting in substantial deaths and morbidity each year. Factors such as mutation and abuse of currently available antibiotics have contributed to the bulk of the menace. Hence, the introduction and implementation of new therapeutic strategies are imperative. Of these strategies, data supporting the role of reactive oxygen species (ROS) in bacterial lethality are intriguing, with several antimicrobials, including antibiotics such as fluoroquinolones, β-lactams, and aminoglycosides, as well as natural plant compounds, being remarkably implicated. Following treatment with ROS-inducing antimicrobials, ROS such as O2•-, OH, and H2O2 generated in bacteria, which the organism is unable to detoxify, damage cellular macromolecules such as proteins, lipids, and nucleic acids and results in cell death. Despite the unique mechanism of action of ROS-inducing antibacterials and significant studies on ROS-mediated means of bacterial killing, the field remains a topical one, with contradicting viewpoints that require frequent review. Here, we appraised the antibacterial agents (antibiotics, natural and synthetic compounds) implicated in ROS generation and the safety concerns associated with their usage. Further, background information on the sources and types of ROS in bacteria, the mechanism of bacterial lethality via oxidative stress, as well as viewpoints on the ROS hypothesis undermining and solidifying this concept are discussed.

Keywords: antibiotic resistance; antioxidants; bacterial lethality; oxidative stress; reactive oxygen species.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents* / metabolism
  • Bacteria / metabolism
  • Hydrogen Peroxide* / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Hydrogen Peroxide
  • Anti-Bacterial Agents
  • Anti-Infective Agents

Grants and funding

The authors specially acknowledge the financial assistance from the Directorate of Research and Postgraduate Support, Durban University of Technology, and the South African Medical Research Council (SA MRC) under a Self-Initiated Research Grant, as well as the National Research Foundation (NRF) Research Development Grant for rated researchers (grant number 120433) to S. Sabiu. The views and opinions expressed are those of the authors and do not necessarily represent the official views of the funders.