Redox Eustress: Roles for Redox-Active Metabolites in Bacterial Signaling and Behavior

Significance: Plant biologists and microbiologists have long discussed and debated the physiological roles of so-called "redox-active metabolites." These are natural products with unusually high redox activity that are not directly required for active growth. Generally, the biological roles of these compounds have been ascribed to interspecies competition and virulence, and they have been considered important sources of distress. Recent Advances: In this review, we discuss two examples of redox-active metabolites: nitric oxide and phenazines. Both are known for their toxic effects in some organisms and conditions but have recently been shown to provide benefits for some organisms under other conditions. Critical Issues: Biologists are identifying new roles for redox-active metabolites that are not directly related to their toxicity. These roles prompt us to suggest a dismissal of the paradigm that all biological stress is negative (i.e., distress). Future Directions: A more accurate view of redox couples requires characterization of their specific biological effects in a condition-dependent manner. The responses to these compounds can be termed "distress" or "eustress," depending on whether they inhibit survival, provide protection from a compound that would otherwise inhibit survival, or promote survival. Antioxid. Redox Signal. 16, 658-667.