Induction of Bacteriophage PinR Facilitates the Evolution of Antibiotic Resistance

Abstract

AbstractA recent work reports that the single treatment of β-lactams can cause a SOS-independent superfast evolution of multi-drug resistance in the DNA repair deficiency Escherichia coli (E. coli), but the mechanism is not yet clear. Here, we find that the induction of PinR, a lambdoid prophage Rac, is involved in this process and facilitates the evolution of antibiotic resistance in DNA repair deficiency bacteria through the repression on the transcription of antioxidative genes and the thereafter ROS burst in cells. It is highlighted that the bacteriophage PinR can orchestrate the mutagenesis induced by the overaccumulation of ROS in cells. More importantly, we for the first time demonstrate that the deletion of pinR can avoid the rapid evolution of antibiotic resistance induced by either the single or long-term exposure to antibiotics, while strategies to target RecA, e.g., the inactivation on RecA, can be safely implemented to disarm the bacterial resistance to other antibiotics. Therefore, from a drug development perspective, our work suggests future studies on the “evolutionary potentiators” towards a safe and more effective strategy to be developed for infectious disease treatment.