Antimicrobial Activity and Cell Selectivity of Synthetic and Biosynthetic Cationic Polymers [PublishAheadOfPrint]

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 -polylysine (PL) is non-cytotoxic to primary human dermal fibroblasts at concentrations up to 2000 μg/ml, suggesting that the presence of isopeptide backbone has greater cell selectivity than α-peptide backbones. Both PL and and linear polyethylenimine (LPEI) exhibit bactericidal properties by depolarizing the cytoplasmic membrane and disrupt the preformed biofilms. PL displays broad spectrum antimicrobial properties against antibiotic-resistant Gram-negative and Gram-positive strains and fungii. PL elicits rapid bactericidal activity against both Gram-negative and Gram-positive bacteria and its biocompatibility index is superior to cationic antiseptic agents and LPEI. PL does not interfere with the wound closure of injured rabbit cornea. In a rabbit model of bacterial keratitis, topical application of PL (0.3% w/v) decreases the bacterial burden and severity of the infections caused by P. aeruginosa and S. aureus strains. In vivo imaging studies confirm that PL treated cornea appeared transparent and non-edematous when compared to untreated infected cornea. Taken together, our results highlight the potential of PL in resolving topical microbial infections.

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