Antibacterial strategies inspired by the oxidative stress and response networks

Abstract

Oxidative stress arises from an imbalance between the excessive accumulation of reactive oxygen species (ROS) and a cell's capability to readily detoxify them. Although ROS are spontaneously generated during the normal oxygen respiration and metabolism, the ROS generation is usually augmented by redox-cycling agents, membrane disrupters, and bactericidal antibiotics, which contributes their antimicrobial bioactivity. It is noted that all the bacteria deploy an arsenal of inducible antioxidant defense systems to cope with the devastating effect exerted by the oxidative stress: these systems include the antioxidant effectors such as catalases and the master regulators such as OxyR. The oxidative stress response is not essential for normal growth, but critical to survive the oxidative stress conditions that the bacterial pathogens may encounter due to the host immune response and/or the antibiotic treatment. Based on these, we here define the ROS-inspired antibacterial strategies to enhance the oxidative stress of ROS generation and/or to compromise the bacterial response of ROS detoxification, by delineating the ROSgenerating antimicrobials and the core concept of the bacterial response against the oxidative stress.

Keywords: OxyR; antibacterial; bactericidal; oxidative stress; reactive oxygen species (ROS); redox cycling; stress response.