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

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.