Antibiotic-persistent bacterial cells exhibiting low-level ROS are eradicated by ROS-independent membrane disruption

The report generalizes the concept that persistence and tolerance involve suppression of toxic metabolites (reactive oxygen species [ROS]). The work also shows that an environmental perturbation (nutrient deprivation) leads to antibiotic tolerance rather than persistence, thereby raising questions about the classification of other environmental perturbations. The synergistic action of multiple aminoglycoside species with polymyxins opens many treatment options. Lethality with biofilms and with <i>S. aureus</i> may extend polymyxin-based therapies beyond planktonic, gram-negative bacteria, and the ROS independence of the combination may allow antioxidant mitigation of drug toxicity. Overall, the work advances our knowledge of persistent and tolerant bacterial pathogens and our efforts to eradicate them.