bm9b00939_si_001.pdf (223.46 kB)
Bacterial Membrane Selective Antimicrobial Peptide-Mimetic Polyurethanes: Structure–Property Correlations and Mechanisms of Action
journal contribution
posted on 2019-10-10, 16:04 authored by Steven Mankoci, Jason Ewing, Punam Dalai, Nita Sahai, Hazel A. Barton, Abraham JoyThe
rise in prevalence of antibiotic resistant strains of bacteria
is a very significant challenge for treating life-threatening infections
worldwide. A source of novel therapeutics that has shown great promise
is a class of biomolecules known as antimicrobial peptides. Previously,
within our laboratories, we developed a new family of water-soluble
antimicrobial polyurethanes that mimic antimicrobial peptides. Within
this current investigation, studies were carried out to gain a greater
understanding of the structure/property relationships of the polyurethanes.
This was achieved by synthesizing a variety of pendant group functionalized
polyurethanes and testing their effectiveness as an antimicrobial
by carrying out minimum inhibitory concentration testing and determining
their compatibility with blood cells. Additionally, insight into the
mode of action of the polyurethanes was obtained through experiments
using dye encapsulated phospholipids and assays of bacterial cells
that indicated the ability of the polyurethanes to penetrate and disrupt
membranes. Collectively, the results indicate that the addition of
hydrophobic, uncharged polar, and anionic moieties do not have a strong
influence on the antimicrobial activity; yet, the addition of hydrophobic
groups enhances cytoplasmic membrane disruption, a larger proportion
of cationic pendant groups promotes greater outer membrane disruption
of Gram negative bacteria, and uncharged polar groups and anionic
groups improve compatibility of the polyurethanes with mammalian cells.