Environmental conditions define the energetics of bacterial dormancy and its antibiotic susceptibility

Abstract

ABSTRACTBacterial cells that halt growth but maintain viability and the capacity to regrow are termed dormant and have been shown to transiently tolerate high concentrations of antimicrobials. Dormancy has been seen in both tolerant and persister cells and is therefore of substantial clinical interest, as both can lead to infection recalcitrance and facilitate the development of antibiotic resistance. In this work, we look at dormancies induced by environmental cues that target different aspects of cell physiology by measuring the energy profiles they elicit in single dormant cells. Our simultaneous measurements of ATP concentration, proton motive force (PMF) and cytoplasmic pH reveal that dormant cells can exist in various energy states, offering a solution to the apparent mutual incompatibility of previous experimental results. We then test whether the energetic makeup is associated with survival to antibiotics of different classes. We find that for certain drugs growth arrest remains the dominant mechanism enabling survival, while for others, like ciprofloxacin, the most energetic cells remain almost untouched by the drug. Our results support a novel relationship between environment and drug susceptibility of dormant cells and suggest that knowledge of the conditions present at the infection site is necessary to design appropriate treatments.