The physiology and biochemistry of oxidative stress in bacteria

Fifty years ago, the discovery of superoxide dismutase revealed that reactive oxygen species (ROS) comprise an unavoidable stress for organisms that dwell in oxic habitats. Since then, workers have gradually pieced together the details. Superoxide and hydrogen peroxide are continuously generated in aerobic cells when oxygen collides with the exposed cofactors of redox enzymes. The rate of electron spillage varies from enzyme to enzyme, and the primary ROS sources have not yet been identified, in any organism. Superoxide and hydrogen peroxide can disrupt key metabolic pathwfays by specifically damaging the iron-sulfur clusters and ferrous cofactors of enzymes. Hydrogen peroxide also threatens DNA, by generating hydroxyl radicals through its oxidation of loose iron. Oxygen-tolerant bacteria successfully suppress these problems by synthesizing high titers of scavenging enzymes. However, hydrogen peroxide can also be formed in the environment, and when it penetrates cells, it can overwhelm basal defenses. Accordingly, it seems universally true that microbes possess specialized transcription factors that detect any rise in peroxide levels and activate tactics to defend their enzymes and DNA. This review describes the chemistry of oxidative stress and the multilayered survival strategies of bacteria. Workers are now focused upon identifying real-world circumstances in which ROS stress is so severe that it becomes bacteriostatic or lethal. Of particular interest is the likelihood that biological warfare leverages ROS through the actions of redox-active antibiotics and cell-based immune responses.