Dynamic helical cationic polyacetylenes for fast and highly efficient killing of bacteria

Wei Zhou; Ge Shi; Peng Zhao; Gai Zhang; Peilang Yang; Bohan Li; Bowen Li; Xinhua Wan; Yijun Zheng

doi:10.1016/j.actbio.2023.02.017

Dynamic helical cationic polyacetylenes for fast and highly efficient killing of bacteria

Acta Biomater. 2023 Apr 15:161:134-143. doi: 10.1016/j.actbio.2023.02.017. Epub 2023 Feb 17.

Authors

Wei Zhou¹, Ge Shi², Peng Zhao¹, Gai Zhang³, Peilang Yang³, Bohan Li¹, Bowen Li⁴, Xinhua Wan⁴, Yijun Zheng⁵

Affiliations

¹ School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.
² Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, China.
³ Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
⁴ Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
⁵ School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address: zhengyj@shanghaitech.edu.cn.

PMID: 36804537
DOI: 10.1016/j.actbio.2023.02.017

Abstract

The antimicrobial activity of native antimicrobial peptides (AMPs) is often attributed to their helical structure, but the effectiveness of synthetic mimics with dynamic helical conformations, such as antimicrobial cationic polymers (ACPs), has not been well studied. Herein we demonstrate the antimicrobial activity of pyrrolidinium-pendant polyacetylenes (PAs) with dynamic helical conformations. The PAs exhibit fast and efficient antimicrobial activity against a wide range of pathogens, with low toxicity to mammalian cells and minimal risk of antibiotic resistance. In addition, the full-thickness wound infection model in mice has demonstrated the favorable biocompatibility and effective in vivo antibacterial capabilities of these PAs. Our data suggest that the dynamic helical structure of these PAs allows them to adapt and form pores in the bacterial membrane upon interaction, leading to their potent antimicrobial activity. This work investigated the antibacterial mechanism of dynamic helical ACPs, which provides valuable guidance for the rational design of high-performance antimicrobial agents. STATEMENT OF SIGNIFICANCE: Our study represents a significant contribution to the literature on antimicrobial cationic polymers (ACPs) as alternatives to antibiotics. Through a systematic investigation of the role of dynamic helical conformation in polyacetylenes (PAs) and the use of PAs with adaptive structure for the first time, we have provided valuable insights into the bacterial membrane action and killing mechanisms of these polymers. The results of our study, including fast killing rates and minimum inhibitory concentrations as low as 4-16 µg/mL against a broad range of pathogens and strong in vivo antibacterial activity, demonstrate the potential of these ACPs as high-performance antimicrobials. Our findings may guide the design of future ACPs with enhanced antimicrobial activity.

Keywords: Antimicrobial cationic polymers; Dynamic helix; Membrane interaction; Polyacetylenes; Secondary structure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Anti-Infective Agents* / pharmacology
Bacteria
Mammals
Mice
Microbial Sensitivity Tests
Polyacetylene Polymer / pharmacology
Polymers / pharmacology

Substances

Polyacetylene Polymer
Anti-Infective Agents
Anti-Bacterial Agents
Polymers