Antibiotic resistance in bacteria: Does a previously de novo acquired antibiotic resistance influences the adaptation to a second antibiotic?

To be able to predict, prevent, or slow down development of antibiotic resistance, the molecular mechanisms that drive acquisition of antibiotic resistance need to be understood. Antibiotic resistance can be induced by stepwise increasing the exposure to the antibiotic. Although each antibiotic class has a specific cellular target, the radical-based theory suggests that as a secondary effect increased levels of cellular reactive oxygen species (ROS) occur as a result of a common pathway. Following this logic, similar mutations might occur in cells with acquired resistance to different bactericidal antibiotics. The effect of resistance associated mutations varies depending on the genetic background, such as the presence of other resistance mutations, a phenomenon known as epistasis.To determine if a previously de novo acquired antibiotic resistance influences the adaptation to a second antibiotic, E. coli populations adapted to either a single or two antibiotics sequentially were analyzed using whole genome sequencing.