Upcycling Poly(ethylene terephthalate) Refuse to Advanced Therapeutics for the Treatment of Nosocomial and Mycobacterial Infections

Abstract

The discovery of antibiotics was one of the crowning achievements of the 20th century, revolutionizing the treatment of infectious disease. However, widespread improper use of antibiotics has led to the development of antibiotic-resistant bacteria, resulting in a healthcare crisis and the urgent need to develop new effective antibiotics. Moreover, current antibiotic therapies are inefficient in treating biofilm-protected and intracellular organisms such as Mycobacterium tuberculosis (Mtb) and non-tuberculous mycobacteria. Herein, we present a strategy for the construction of macromolecular antimicrobial compounds using a catalyst-free, polyaddition polymerization process of monomers derived from poly(ethylene terephthalate) (PET) refuse. The initial depolymerization of PET refuse via aminolysis is highly amenable and scalable process to access a broad array of functional tertiary amine-containing terephthalamide polymer-grade monomers. This new monomer platform was subsequently used to construct antimicrobial cationic polyionenes via a polyaddition polymerization. The composition and structure of the antimicrobial polyionenes were varied to study their antimicrobial activity against a broad spectrum of pathogenic microbes including Mtb. Polymers with optimized compositions have potent antimicrobial activity with low minimum inhibitory concentrations of 3.9-15.8 μg/mL against microbes including Mtb and high selectivity for microbes over mammalian cells. Similarly, activity against Mtb ranged from 2 to 16 μg/mL, while values for Mycobacterium avium and Mycobacterium abscessus were higher. In addition, antimicrobial polyionenes were able to target and kill M. avium residing inside human macrophages. Overall, PET refuse was successfully used as a feedstock to generate new functional terephthalamide monomers for new macromolecular antimicrobial polyionenes. These polyionenes are promising candidate agents to treat difficult-to-treat bacterial and mycobacterial infections that are currently resistant to existing antibiotics.