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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 ?-polylysine (?PL) is noncytotoxic to primary human dermal fibroblasts at concentrations of up to 2,000 ?g/ml, suggesting that the presence of an isopeptide backbone has greater cell selectivity than the presence of ?-peptide backbones. Both ?PL and linear polyethylenimine (LPEI) exhibit bactericidal properties by depolarizing the cytoplasmic membrane and disrupt preformed biofilms. ?PL displays broad-spectrum antimicrobial properties against antibiotic-resistant Gram-negative and Gram-positive strains and fungi. ?PL 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. ?PL does not interfere with the wound closure of injured rabbit corneas. In a rabbit model of bacterial keratitis, the topical application of ?PL (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 ?PL-treated corneas appeared transparent and nonedematous compared to untreated infected corneas. Taken together, our results highlight the potential of ?PL in resolving topical microbial infections.

SUBMITTER: Venkatesh M

PROVIDER: S-EPMC5610535 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Antimicrobial Activity and Cell Selectivity of Synthetic and Biosynthetic Cationic Polymers.

Venkatesh Mayandi M Barathi Veluchamy Amutha VA Goh Eunice Tze Leng ETL Anggara Raditya R Fazil Mobashar Hussain Urf Turabe MHUT Ng Alice Jie Ying AJY Harini Sriram S Aung Thet Tun TT Fox Stephen John SJ Liu Shouping S Yang Liang L Barkham Timothy Mark Sebastian TMS Loh Xian Jun XJ Verma Navin Kumar NK Beuerman Roger W RW Lakshminarayanan Rajamani R

Antimicrobial agents and chemotherapy 20170922 10

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 pre ...[more]

PMID: 28784676

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Project description:Photodynamic inactivation is a rapidly developing antimicrobial treatment that employs a nontoxic photoactivatable dye or photosensitizer in combination with harmless visible light to generate reactive oxygen species that are toxic to cells. Tetrapyrroles (e.g., porphyrins, chlorins, bacteriochlorins) are a class of photosensitizers that exhibit promising characteristics to serve as broad-spectrum antimicrobials. In order to bind to and efficiently penetrate into all classes of microbial cells, tetrapyrroles should have structures that contain (i) one or more cationic charge(s) or (ii) a basic group. In this report, we investigate the use of new stable synthetic bacteriochlorins that have a strong absorption band in the range 720 to 740 nm, which is in the near-infrared spectral region. Four bacteriochlorins with 2, 4, or 6 quaternized ammonium groups or 2 basic amine groups were compared for light-mediated killing against a gram-positive bacterium (Staphylococcus aureus), a gram-negative bacterium (Escherichia coli), and a dimorphic fungal yeast (Candida albicans). Selectivity was assessed by determining phototoxicity against human HeLa cancer cells under the same conditions. All four compounds were highly active (6 logs of killing at 1 microM or less) against S. aureus and showed selectivity for bacteria over human cells. Increasing the cationic charge increased activity against E. coli. Only the compound with basic groups was highly active against C. albicans. Supporting photochemical and theoretical characterization studies indicate that (i) the four bacteriochlorins have comparable photophysical features in homogeneous solution and (ii) the anticipated redox characteristics do not correlate with cell-killing ability. These results support the interpretation that the disparate biological activities observed stem from cellular binding and localization effects rather than intrinsic electronic properties. These findings further establish cationic bacteriochlorins as extremely active and selective near-infrared activated antimicrobial photosensitizers, and the results provide fundamental information on structure-activity relationships for antimicrobial photosensitizers.

Dataset Information

Antimicrobial Activity and Cell Selectivity of Synthetic and Biosynthetic Cationic Polymers.

Publications

Antimicrobial Activity and Cell Selectivity of Synthetic and Biosynthetic Cationic Polymers.

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