Structural engineering of antimicrobials for optimal broad-spectrum activity

Abstract

Antimicrobial materials are a crucial component in eradicating and managing the spread of infectious diseases. They are expected to act on a broad-spectrum of microbes, including emerging pathogens which could cause the next Disease X. Herein, we reassessed a series of antimicrobial imidazolium polymers on our shelves and uncovered extended functionality through dual modes of action. By redesigning their structures, a truly broad-spectrum antimicrobial material with optimized activity against bacteria (G ​+ve, G -ve) and fungi, as well as enveloped and non-enveloped viruses was developed. We demonstrated that the imidazolium polymer exhibits dual modes of function against microbes: targeting the microbial membrane and binding DNA. The latter DNA binding affinity was found to be key against non-enveloped viruses. With this insight, we designed small molecule compounds that exhibited optimum broad-spectrum antimicrobial activity and excellent efficacy against ESKAPE group of pathogens that are responsible for some of the deadliest nosocomial infections worldwide. Our results could also shed light on the design of broad-spectrum antimicrobial compounds against Disease X.