Influence of Reactive Oxygen Species onDe NovoAcquisition of Resistance to Bactericidal Antibiotics

The radical-based theory proposes that three major classes of bactericidal antibiotics, i.e., β-lactams, quinolones, and aminoglycosides, have in common the downstream formation of lethal levels of reactive oxygen species (ROS) as part of the killing mechanism. If bactericidal antibiotics exhibit a common mechanism, then it is to be expected that the acquisition of resistance against these drugs would have some shared traits as well. Indeed, cells made resistant to one bactericidal antibiotic more rapidly became resistant to another. This effect was absent after induced resistance to a bacteriostatic drug.De novo acquisition of resistance to one bactericidal antibiotic provided partial protection to killing by bactericidal antibiotics from a different class. This protective effect was observed in short-term experiments. No protective effect was detected during 24-h exposures, suggesting that cross-resistance did not occur. In the wild-type strain, exposure to bactericidal antibiotics increased intracellular ROS levels. This increase in ROS levels was not observed when strains resistant to these drugs were exposed to the same concentrations. These results indicate thatde novo acquisition of resistance to the bactericidal drugs tested involves a common cellular response that provides protection against ROS accumulation upon exposure to this type of antibiotics. A central mechanism or at least a few common elements within the separate mechanisms possibly play a role during the acquisition of antibiotic resistance.