A molecular architectural design that promises potent antimicrobial activity against multidrug-resistant pathogens

Year: 2021

Type: article

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., PEG12k–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.

Source: NPG Asia Materials

DOI: 10.1038/s41427-021-00287-y

Authors: Bing Yuan, Jiaojiao Liu, Zhixiong Deng, Lin Wei, Wenwen Li, Yujiang Dou, Zhonglan Chen, Che Zhang, Yu Xia, Jing Wang, Mengling Zhang, Kai Yang, Yuqiang Ma, Zhenhui Kang

Institutions: Soochow University, Suzhou University of Technology, National Laboratory of Solid State Microstructures, Nanjing University, Northeast Normal University

Language: English

Topic: Antimicrobial Peptides and Activities

Subfield: Microbiology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,990

Funders: National Natural Science Foundation of China, Government of Jiangsu Province, Natural Science Foundation of Jiangsu Province, Priority Academic Program Development of Jiangsu Higher Education Institutions, Higher Education Discipline Innovation Project

OpenAlex ID: W3133919798