Antimicrobial Activity and Cell Selectivity of Synthetic and Biosynthetic Cationic Polymers.
| Autor: | Venkatesh M; Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore., Barathi VA; Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore.; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore., Goh ETL; Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore., Anggara R; Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore., Fazil MHUT; Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building, Singapore., Ng AJY; Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore., Harini S; Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore., Aung TT; Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore., Fox SJ; Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore., Liu S; Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore.; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore., Yang L; Singapore Centre for Environmental Life Sciences, Nanyang Technological University, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore., Barkham TMS; Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore., Loh XJ; Institute of Materials Research and Engineering, A*STAR, Singapore., Verma NK; Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building, Singapore nkverma@ntu.edu.sg roger.wilmer.beuerman@seri.com.sg lakshminarayanan.rajamani@seri.com.sg., Beuerman RW; Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore nkverma@ntu.edu.sg roger.wilmer.beuerman@seri.com.sg lakshminarayanan.rajamani@seri.com.sg.; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore., Lakshminarayanan R; Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore nkverma@ntu.edu.sg roger.wilmer.beuerman@seri.com.sg lakshminarayanan.rajamani@seri.com.sg.; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore. |
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| Jazyk: | angličtina |
| Zdroj: | Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2017 Sep 22; Vol. 61 (10). Date of Electronic Publication: 2017 Sep 22 (Print Publication: 2017). |
| DOI: | 10.1128/AAC.00469-17 |
| Abstrakt: | 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. (Copyright © 2017 Venkatesh et al.) |
| Databáze: | MEDLINE |
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