3.8 Article

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

期刊

ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 7, 期 9, 页码 4659-4668

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.1c00856

关键词

biomass valorization; lignocellulose; quaternization; antibacterial resistance; mechanism of action

资金

  1. A*STAR (Agency for Science, Technology and Research), Singapore
  2. Singapore Ministry of Health's National Medical Research Council under its Centre Grant Programme.Optimization of Core Platform Technologies for Ocular Research (INCEPTOR) [NMRC/CG/M010/2017_SERI]
  3. SingHealth Foundation [SHF/FG663P/2017]
  4. Agency for Science, Technology and Research (A*STAR)

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The study found that hyperbranched copolymers with cationic charges have strong antimicrobial effects against resistant bacterial strains without inducing resistance. These copolymers target the outer membrane, providing valuable insights for future antibiotic development.
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. Coli ATCC 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.

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