作者
Wenbin Zhong, Zhenyu Shi, Surendra H Mahadevegowda, Bo Liu, Kaixi Zhang, Chong Hui Koh, Lin Ruan, Yahua Chen, Merve S Zeden, Carmen JE Pee, Kalisvar Marimuthu, Partha Pratim De, Oon Tek Ng, Yabin Zhu, Yonggui Robin Chi, Paula T Hammond, Liang Yang, Yunn-Hwen Gan, Kevin Pethe, E Peter Greenberg, Angelika Gründling, Mary B Chan-Park
发表日期
2020/12/8
期刊
Proceedings of the National Academy of Sciences
卷号
117
期号
49
页码范围
31376-31385
出版商
National Academy of Sciences
简介
For a myriad of different reasons most antimicrobial peptides (AMPs) have failed to reach clinical application. Different AMPs have different shortcomings including but not limited to toxicity issues, potency, limited spectrum of activity, or reduced activity in situ. We synthesized several cationic peptide mimics, main-chain cationic polyimidazoliums (PIMs), and discovered that, although select PIMs show little acute mammalian cell toxicity, they are potent broad-spectrum antibiotics with activity against even pan-antibiotic-resistant gram-positive and gram-negative bacteria, and mycobacteria. We selected PIM1, a particularly potent PIM, for mechanistic studies. Our experiments indicate PIM1 binds bacterial cell membranes by hydrophobic and electrostatic interactions, enters cells, and ultimately kills bacteria. Unlike cationic AMPs, such as colistin (CST), PIM1 does not permeabilize cell membranes. We show that a …
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