A better understanding of the impact of antibiotics on bacteria is required to increase the efficiency of antibiotic treatments and to slow the emergence of resistance. Using Escherichia coli, we examined how bacteria exposed to sublethal concentrations of ampicillin adjust gene expression patterns and metabolism to simultaneously deal with the antibiotic-induced damage and maintain rapid growth. We found that the treated cells increased energy production, as well as translation and macromolecular repair and protection. These responses are adaptive, because they confer increased survival not only to lethal ampicillin treatment but also to non-antibiotic lethal stresses. This robustness is modulated by nutrient availability. Because different antibiotics and other stressors induce the same set of responses, we propose that it constitutes a general core hormetic stress response. It is plausible that this response plays an important role in the robustness of bacteria exposed to antibiotic treatments and constant environmental fluctuations in natural environments.

SignificanceAntibiotic resistance leads to substantial mortality and morbidity and significant economic cost because it seriously undermines our ability to treat bacterial infections. Therefore, a better understanding of the effect of antibiotics on bacteria is needed to increase the effectiveness of treatments and slow the emergence of resistance. The bactericidal effects of antibiotics are triggered by target-specific interactions, but there is growing evidence that an important part of their cytotoxicity results from metabolic disturbances induced by treatment. In this article, we report that the perturbation of DNA replication by a wide-spectrum antibiotic, trimethoprim, affects bacterial metabolism, which provokes the production of genotoxic agents and DNA damage, whose processing ultimately contributes to cell death under both aerobic and anaerobic conditions.