In:
NPG Asia Materials, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
Abstract:
Addressing the devastating threat of drug-resistant pathogens requires the discovery of new antibiotics with advanced action mechanisms and/or novel strategies for drug design. Herein, from a biophysical perspective, we design a class of synthetic antibacterial complexes with specialized architectures based on melittin (Mel), a natural antimicrobial peptide, and poly(ethylene glycol) (PEG), a clinically available agent, as building blocks that show potent and architecture-modulated antibacterial activity. Among the complexes, the flexibly linear complex consisting of one Mel terminally connected with a long-chained PEG (e.g., PEG 12k –1*Mel) shows the most pronounced improvement in performance compared with pristine Mel, with up to 500% improvement in antimicrobial efficiency, excellent in vitro activity against multidrug-resistant pathogens (over a range of minimal inhibitory concentrations of 2–32 µg mL −1 ), a 68% decrease in in vitro cytotoxicity, and a 57% decrease in in vivo acute toxicity. A lipid-specific mode of action in membrane recognition and an accelerated “channel” effect in perforating the bacterial membrane of the complex are described. Our results introduce a new way to design highly efficient and low-toxicity antimicrobial drugs based on architectural modulations with clinically available agents.
Type of Medium:
Online Resource
ISSN:
1884-4049
,
1884-4057
DOI:
10.1038/s41427-021-00287-y
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2608333-4
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