Polyacrylamide-based Antimicrobial Copolymers Immune to Typical Resistance Mechanisms to Replace or Rescue Antibiotics
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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.
BIGGER PICTURE
Antibiotics save countless lives each year and have dramatically improved human health outcomes since their introduction in the 20 th century. Unfortunately, bacteria are now developing resistance to antibiotics at an alarming rate, with many new strains of “superbugs” showing simultaneous resistance to multiple classes of antibiotics. To combat this growing crisis, we must develop new antibiotics that can overcome typical resistance mechanisms. Copolymer drugs such as the ones presented in this paper can delay or prevent the development of resistance and rehabilitate existing antibiotics by improving their potency and limiting the ability of bacteria to develop resistance. This work represents a significant step towards combatting antimicrobial resistance.
