Priestia megaterium cells are primed for surviving lethal doses of antibiotics and chemical stress.

Antibiotic resistant infections kill millions worldwide yearly. However, a key factor in recurrent infections is antibiotic persisters. Persisters are not inherently antibiotic-resistant but can withstand antibiotic exposure by entering a non-dividing state. This tolerance often results in prolonged antibiotic usage, increasing the likelihood of developing resistant strains. Here, we show the existence of "primed cells" in the Gram-positive bacterium Priestia megaterium, formerly known as Bacillus megaterium. These cells are pre-adapted to become persisters prior to lethal antibiotic stress. Remarkably, this prepared state is passed down through multiple generations via epigenetic memory, enhancing survival against antibiotics and other chemical stress. Previously, two distinct types of persisters were proposed: Type I and Type II, formed during stationary and log phases, respectively. However, our findings reveal that primed cells contribute to an increase in persisters during transition and stationary phases, with no evidence supporting distinct phenotypes between Type I and Type II persisters.