Abstract
It was recently reported that the production of Reactive Oxygen Species (ROS) is a common mechanism of cell death induced by bactericidal antibiotics. Here we show that triggering the Escherichia coli chromosomal toxin–antitoxin system mazEF is an additional determinant in the mode of action of some antibiotics. We treated E. coli cultures by antibiotics belonging to one of two groups: (i) Inhibitors of transcription and/or translation, and (ii) DNA damaging. We found that antibiotics of both groups caused: (i) mazEF-mediated cell death, and (ii) the production of ROS through MazF action. However, only antibiotics of the first group caused mazEF-mediated cell death that is ROS-dependent, whereas those of the second group caused mazEF-mediated cell death by an ROS-independent pathway. Furthermore, our results showed that the mode of action of antibiotics was determined by the ability of E. coli cells to communicate through the signaling molecule Extracellular Death Factor (EDF) participating in mazEF induction.
Highlights
Antibiotics are classed as either ‘‘bactericidal,’’ meaning that they can kill bacteria, or ‘‘bacteriostatic,’’ meaning that they can only inhibit bacterial growth
We have previously shown that some antibiotics trigger cell death by the activation of the built-in death system mazEF of Escherichia coli [4,5,6]. mazEF is a toxin–antitoxin (TA) module found on the chromosomes of many bacteria, including pathogens [7,8,9,10]
The modes of action of antibiotics are mainly characterized by the effect they have on their targets
Summary
Antibiotics are classed as either ‘‘bactericidal,’’ meaning that they can kill bacteria, or ‘‘bacteriostatic,’’ meaning that they can only inhibit bacterial growth. Bacteriostatic drugs may be effective, because inhibiting bacterial growth allows the body’s defence mechanisms to eliminate the pathogenic bacteria [1]. The mechanisms of antibiotics actions were well studied, in relation to their targets interactions. They fall into three main groups: DNA damage-causing agents, inhibitors of protein synthesis, and inhibitors of cell wall turnover [2]. It was shown that the three major groups of bactericidal antibiotics, regardless of their targets interactions, stimulate the production of hydroxyl radicals in Gram-negative and Gram-positive bacteria, which causes cell death. The bacteriostatic antibiotics do not produce hydroxyl radicals [3]
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