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Review
. 2014 Oct:21:1-6.
doi: 10.1016/j.mib.2014.06.008. Epub 2014 Jul 30.

Reactive oxygen species and the bacterial response to lethal stress

Xilin Zhao  1 , Karl Drlica  2
Affiliations
Review

Reactive oxygen species and the bacterial response to lethal stress

Xilin Zhao et al. Curr Opin Microbiol. 2014 Oct.

Abstract

Bacteria are killed by a variety of lethal stressors, some of which promote a cascade of reactive oxygen species (ROS). Perturbations expected to alter ROS accumulation affect the lethal action of diverse antibacterials, leading to the hypothesis that killing by these agents can involve ROS-mediated self-destruction. Recent challenges to the hypothesis are considered, particularly with respect to complexities in assays that distinguish primary damage from the cellular response to that damage. Also considered are bifunctional factors that are protective at low stress levels but destructive at high levels. These considerations, plus new data, support an involvement of ROS in the lethal action of some antimicrobials and raise important questions concerning consumption of antioxidant dietary supplements during antimicrobial chemotherapy.

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Figures

Figure 1
Figure 1
Stress-induced ROS and the live-or-die bacterial stress response. Stress, such as exposure to lethal antibiotics, generates stressor-specific primary lesions (a) that activate toxin-antitoxin modules (TA, for example MazEF, (b)). Toxin-mediated mRNA cleavage may lead to production of truncated, misfolded peptides that lodge in cell membranes and induce the two-component Cpx envelope stress system (c). Induction of Cpx up-regulates expression of YihE protein kinase (d), which mitigates MazF toxin activity (e). Induction of Cpx can also induce expression of genes encoding proteins that refold and degrade misfolded peptides and suppress Cpx induction (f). Cpx activation and membrane perturbation may activate the Arc two-component system (g), which raises ROS levels (h), possibly through stimulation of the TCA cycle and interference with cytochrome bd oxidase [27,28]. Elevated levels of ROS can induce the SoxRS-MarRAB-AcrAB efflux pump system (i) that exports toxic stressors and thereby suppresses primary lesion formation (j). ROS accumulation also induces the SoxRS-OxyRS regulons (k) that interfere with (l) ROS generating secondary cellular damage (m). Secondary damage, if uncontrolled, is expected to stimulate successive rounds of ROS production (n) that kill cells (o), thereby removing severely damaged cells from bacterial populations.
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