Persisters are dormant antibiotic-tolerant cells that usually compose a small fraction of bacterial populations. In this work, we focused on the role of trehalose in persister formation. We found that the Δ mutant, which is unable to synthesize trehalose, produced increased levels of persisters in the early stationary phase and under heat stress conditions. The lack of trehalose in the Δ mutant resulted in oxidative stress, manifested by increased membrane lipid peroxidation after heat shock. Stationary Δ cells additionally exhibited increased levels of oxidized proteins and apurinic/apyrimidinic sites in DNA as compared to WT cells. Oxidative stress caused by the lack of trehalose was accompanied by the overproduction of extracellular indole, a signal molecule that has been shown to stimulate persister formation. Our major conclusion is that intracellular trehalose protects cells against oxidative stress and limits indole synthesis, which in turn inhibits the formation of persisters.


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