Implications of bacterial exposure to reactive oxygen and chlorine species.

To inhabit aerobic environments, microbes must be able to cope with the reactive byproducts of aerobic growth. These toxic compounds, also named reactive oxygen species (ROS), damage a variety of cellular macromolecules, and thus demand universal adaptive responses in microorganisms. Beyond ROS, microbes must also contend with exogenous oxidants such as reactive chlorine species (RCS) and reactive nitrogen species (RNS). In the context of antimicrobial activity, discussions on exogenous reactive species have typically focused on pathogen clearance during the oxidative burst of activated leukocytes. However, the discovery that oxidative stress may contribute to the activity of bactericidal antibiotics presents new possibilities for targeting the antioxidant defenses of pathogens as an antimicrobial strategy for potentiating current antibiotics. Considering the emergence of antibiotic resistance in many clinically relevant bacteria, and the concurrent decline in antibiotic discovery efforts, such alternative treatment options are increasingly needed. In this minireview, we discuss the well-established pathways of oxidative stress resulting from endogenous and exogenous sources of ROS and RCS. We also contrast the macromolecular targets of ROS and RCS, as well as specialized detoxification mechanisms evolved by bacteria to minimize damage caused by each species. The implications of ROS/RCS exposure are then discussed in two facets: their contributions to antibiotic resistance and involvement in the activity of bactericidal antibiotics. Finally, we highlight antimicrobial strategies whose mode of action is proposed to depend on or involve ROS formation.