Cationic Lignin-Based Hyperbranched Polymers to Circumvent Drug Resistance in Pseudomonas Keratitis

ACS Biomater Sci Eng. 2021 Sep 13;7(9):4659-4668. doi: 10.1021/acsbiomaterials.1c00856. Epub 2021 Aug 20.

Abstract

The rise of antimicrobial-resistant bacteria strains has been a global public health concern due to their ability to cause increased patient morbidity and a greater burden on the healthcare system. As one of the potential solutions to overcome such bacterial infections, hyperbranched copolymers with cationic charges were developed. These copolymers were assessed for their antimicrobial efficacy and their bactericidal mechanisms. They were found to be potent against mobile colistin-resistant 1 strains, which was significant as colistin is known to be the last-resort antibiotic against Gram-negative bacteria. Furthermore, there was no sign of mutational resistance developed by E. ColiATCC 25922 and MCR 1+E. Coli against the copolymer even up to 20 passages. The ability to evade inducing resistance would provide invaluable insights for future antibiotic development. Our studies suggest that the bactericidal efficacy comes from the ability to target the outer membrane efficaciously. In vivo study using a Pseudomonas keratitis model showed that the copolymer was compatible with the eye and further supported that the copolymer treatment was effective for complete bacteria elimination.

Keywords: antibacterial resistance; biomass valorization; lignocellulose; mechanism of action; quaternization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Resistance
  • Escherichia coli
  • Humans
  • Keratitis* / drug therapy
  • Lignin*
  • Polymers
  • Pseudomonas

Substances

  • Polymers
  • Lignin