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.

The contribution of toxin-antitoxin systems to the persistence of bacteria to antibiotics has been intensively studied. This is also the case with the E. coli TisB/IstR toxin-antitoxin system, but the contribution of TisB to the persistence to antibiotics turned out to be not as straightforward as anticipated.