Williams, S. C.; Chosy, M. B.; Jons, C. K.; Dong, C.; Prossnitz, A. N.; Liu, X.; Lopez Hernandez, H.; Cegelski, L.; Appel, E.

To mitigate the global burden of antimicrobial resistance, we must develop antibiotics that are broadly effective, safe, and highly stable for the purpose of global access. In this manuscript, we report the development of polyacrylamide-based copolymers as a novel class of broad-spectrum antibiotics with efficacy against several critical pathogens. We demonstrate that these copolymer drugs are selective for bacteria over mammalian cells, indicating a favorable safety profile. We show that they kill bacteria through a membrane disruption mechanism, which allows them to overcome traditional mechanisms of antimicrobial resistance. Lastly, we demonstrate their ability to rehabilitate an existing small-molecule antibiotic that is highly subject to resistance development by improving its potency and eliminating the development of resistance in a combination treatment.