Mechanism and antibacterial synergies of poly(Dabco-BBAC) nanoparticles against multi-drug resistant Pseudomonas aeruginosa isolates from human burns

Bioorg Chem. 2023 Nov:140:106718. doi: 10.1016/j.bioorg.2023.106718. Epub 2023 Jul 11.

Abstract

Multi-drug resistant bacteria are a major problem in the treatment of infectious diseases, such as pneumonia, meningitis, or even coronavirus disease 2019 (COVID-19). Cationic nanopolymers are a new type of antimicrobial agent with high efficiency. We synthesized and characterized cationic polymer based on 1,4-diazabicyclo [2.2.2] octane (DABCO) and Bis (bromoacetyl)cystamine (BBAC), named poly (DABCO-BBAC) nanoparticles(NPs), and produced 150 nm diameter NPs. The antibacterial activity of poly (DABCO-BBAC) against eight multi drug resistant (MDR) Pseudomonas aeruginosa isolates from human burns, its possible synergistic effect with gentamicin, and the mechanism of action were examined. Poly(DABCO-BBAC) could effectively inhibit and kill bacterial strains at a very low concentration calculated by minimum inhibitory concentration (MIC) assay. Nevertheless, its synergism index with gentamicin showed an indifferent effect. Moreover, transmission electron microscopy and lipid peroxidation assays showed that poly (DABCO-BBAC) distorted and damaged the bacterial cell wall. These results suggest that the poly (DABCO-BBAC) could be an effective antibacterial agent for MDR clinical pathogens.

Keywords: Antibacterial mechanism; Antibiotic synergism; Cationic nanopolymer; Multi-drug resistance, Poly(DABCO_BBAC) nanoparticles; Nanomedicine; Pseudomonas aeruginosa.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Burns*
  • COVID-19*
  • Gentamicins / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Nanoparticles*
  • Pseudomonas aeruginosa

Substances

  • triethylenediamine
  • Anti-Bacterial Agents
  • Gentamicins