Anticipating the evolution of resistance to emerging antibiotic candidates

Interviewer: Today, we are joined by Dr. Ana Martins from the Biological Research Center in Szeged, Hungary to discuss her recent publication in Science Translational Medicine. In her paper, Ana demonstrates that many antibiotic candidates for gram-positive infections rapidly induce multi-drug resistance in Staphylococcus aureus, raising concerns about their long-term efficacy. Ana, thank you very much for joining us today. Dr. Martins: Thank you for inviting me. Interviewer: So to start, can you describe the key findings from your paper regarding the evolution of resistance in Staphylococcus aureus, and how these findings challenge current strategies in antibiotic development. Dr. Martins: One of our key findings is that resistance can evolve even against new antibiotic candidates. So this was true for antibiotics that share a target with antibiotics currently in use, but also for new molecules with possible multi-target effects on the cell envelope, for example. We also discovered that some mutations conferring resistance to these new molecules are already present in the clinical isolates of strains resistant to antibiotics in use. However, one surprising finding was with a repurposed drug that targets multiple distinct cellular functions, and in this case, resistance evolution was not observed. In short, these were the main results. Interviewer: The study provides evidence of two specific mechanisms of acquiring resistance. That is, the selection of resistant variants