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The newly discovered extracellular death factor (EDF) is a pentapeptide with the sequence NNWNN in  Escherichia coli . It was reported that it participated in the cell death process mediated by toxin-antitoxin system  mazEF . Reactive oxygen species (ROS) are recently considered as common factors for bactericidal antibiotics-mediated cell death. Previous study indicated that EDF could scavenge hydroxyl radicals and might act as a signal molecule with dual effects, “death” and “survival”. But the structure-activity relationship of EDF and the effects of EDF on the activity of antibiotics remain unclear. In the present study, our results indicated that tryptophan could be the key residue to the hydroxyl radicals-scavenging activity of EDF, and EDF could protect  Escherichia coli  from killing by bactericidal antibiotics, but not by DNA-damaging or bacteriostatic antibiotics. Our results could provide novel evidence to understand the role of EDF in drug-resistance.

The extracellular death factor (EDF) protects Escherichia coli by scavenging hydroxyl radicals induced by bactericidal antibiotics