Antimicrobial Activity and Cell Selectivity of Synthetic and Biosynthetic Cationic Polymers

Abstract

The mammalian and microbial cell selectivity of synthetic and biosynthetic cationic polymers has been investigated. Among the polymers with peptide backbones, polymers containing amino side chains display greater antimicrobial activity than those with guanidine side chains, whereas ethylenimines display superior activity over allylamines. The biosynthetic polymer ε-polylysine (εPL) is noncytotoxic to primary human dermal fibroblasts at concentrations of up to 2,000 μg/ml, suggesting that the presence of an isopeptide backbone has greater cell selectivity than the presence of α-peptide backbones. Both εPL and linear polyethylenimine (LPEI) exhibit bactericidal properties by depolarizing the cytoplasmic membrane and disrupt preformed biofilms. εPL displays broad-spectrum antimicrobial properties against antibiotic-resistant Gram-negative and Gram-positive strains and fungi. εPL elicits rapid bactericidal activity against both Gram-negative and Gram-positive bacteria, and its biocompatibility index is superior to those of cationic antiseptic agents and LPEI. εPL does not interfere with the wound closure of injured rabbit corneas. In a rabbit model of bacterial keratitis, the topical application of εPL (0.3%, wt/vol) decreases the bacterial burden and severity of infections caused by Pseudomonas aeruginosa and Staphylococcus aureus strains. In vivo imaging studies confirm that εPL-treated corneas appeared transparent and nonedematous compared to untreated infected corneas. Taken together, our results highlight the potential of εPL in resolving topical microbial infections.

Nucleic acid peptide nanogels for the treatment of bacterial keratitis

“…26,44,58 At 48 h post-inoculation the mean corneal thickness continued to increase for the control group (194.4 ± 27.4 μm) which indicates increased severity of the infection. 59 An even more intense reduction in the average corneal thickness was seen in the 0.15% pre-loaded L12 nanogel (112.7 ± 29.6 μm), 0.3% preloaded L12 nanogel (117.2 ± 8.7 μm) and 0.3% gatifloxacin (124.3 ± 18.7 μm) treated groups after 48 h.…”

Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates: In Vivo Virulence Assessment in Galleria mellonella and Potential Therapeutics by Polycationic Oligoethyleneimine

“…The polymer design and the polymer-membrane interactions are crucial issues for bacterial infection eradication. In a recent study, linear and branched PEI polymers were found to have very similar MIC values, while ε-polycaprolactone showed superior broad-spectrum antimicrobial properties over L-PEI [ 46 ]. Hence, in future work we will consider the use of a coarse-grain (CG) molecular dynamics model of L-OEI-h to better understand its interactions with bacterial and mammalian membranes.…”

An Smp43-Derived Short-Chain α-Helical Peptide Displays a Unique Sequence and Possesses Antimicrobial Activity against Both Gram-Positive and Gram-Negative Bacteria

“…Membrane depolarization was monitored by using the cell membrane potential sensitive probe DiSC 3 -5 (Sigma, USA) [ 77 , 78 ]. Briefly, the bacterial cells were washed and diluted with 4-(2-hydroxyerhyl) piperazine-1-erhanesulfonic acid (HEPES), buffer (5 mM HEPES, 20 mM glucose, 100 mM potassium chloride, pH 7.4) to achieve a concentration of OD 630 = 0.05, and prepared in a 96-well polypropylene microtiter plate.…”