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. 2025 Aug 9:10.1007/82_2024_284.
doi: 10.1007/82_2024_284. Online ahead of print.

Antibiotic-Induced Bacterial Cell Death: A "Radical" Way of Dying?

Parsa Alba Farhang  1 , Katherine L Cotten  1 , Jamie C Smith  1 , Kimberly M Davis  2
Affiliations

Antibiotic-Induced Bacterial Cell Death: A "Radical" Way of Dying?

Parsa Alba Farhang et al. Curr Top Microbiol Immunol. .

Abstract

The rising prevalence of antibiotic resistance is rendering certain antibiotics ineffective in treating bacterial infections of public health importance. Deepening our understanding of how these drugs induce bacterial cell death, and whether antibiotics trigger a cell death program compared to direct killing, could help generate novel antibiotics or modify existing therapeutic approaches to improve clinical outcomes. Among the most widely used bactericidal antibiotics (beta-lactams, aminoglycosides, and fluoroquinolones), the primary drug-target interactions, and how they induce cell death, are well characterized. Additionally, there has been a recent debate as to whether a generalized bacterial cell death mechanism exists, shared among bactericidal antibiotics. The hypothesized mechanism, referred to as the common reactive oxygen species (ROS) pathway in this chapter, argues that certain bactericidal antibiotics have off-target effects that increase ROS generation in an iron- and oxygen-dependent manner. Moreover, this spike in ROS is thought to also contribute to induced bacterial cell death. Here we will discuss the target-specific mechanisms of distinct classes of bactericidal antibiotics, how these promote bacterial cell death, and the data that both support and refute the existence of a common cell death pathway.

Keywords: Aminoglycosides; Antibiotics; Bactericidal; Beta-lactams; Fluoroquinolones; Reactive oxygen species.

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Conflict of interest statement

Authorship. PAF drafted the initial outline of this manuscript and wrote the first draft. KLC and JCS wrote specific sections of the manuscript and PAF, KLC, JCS, and KMD all edited the manuscript. All authors approved the manuscript. Declaration of Interest: The authors of this manuscript declare no conflicts of interest.

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