Host-Defense-Peptide-Mimicking β-Peptide Polymer Acting as a Dual-Modal Antibacterial Agent by Interfering Quorum Sensing and Killing Individual Bacteria Simultaneously
Wanlin Li,
Ximian Xiao,
Yuchen Qi,
Xiuhui Lin,
Huiqun Hu,
Minqi Shi,
Min Zhou,
Weinan Jiang,
Longqiang Liu,
Kang Chen,
Kai Wang,
Runhui Liu,
Min Zhou
Affiliations
Wanlin Li
Department of Respiratory and Critical Care Medicine, the Fourth Affiliated Hospital,
Zhejiang University School of Medicine, Yiwu 223300, China.
Ximian Xiao
State Key Laboratory of Bioreactor Engineering, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering,
East China University of Science and Technology, Shanghai 200237, China.
Yuchen Qi
Institute of Translational Medicine,
Zhejiang University, Hangzhou 310029, China.
Xiuhui Lin
Department of Infectious Diseases, The Second Affiliated Hospital,
Zhejiang University School of Medicine, Hangzhou 310058, China
Huiqun Hu
Department of Infectious Diseases, The Second Affiliated Hospital,
Zhejiang University School of Medicine, Hangzhou 310058, China
Minqi Shi
Institute of Translational Medicine,
Zhejiang University, Hangzhou 310029, China.
Min Zhou
State Key Laboratory of Bioreactor Engineering, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering,
East China University of Science and Technology, Shanghai 200237, China.
Weinan Jiang
State Key Laboratory of Bioreactor Engineering, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering,
East China University of Science and Technology, Shanghai 200237, China.
Longqiang Liu
State Key Laboratory of Bioreactor Engineering, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering,
East China University of Science and Technology, Shanghai 200237, China.
Kang Chen
State Key Laboratory of Bioreactor Engineering, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering,
East China University of Science and Technology, Shanghai 200237, China.
Kai Wang
University-University of Edinburgh Institute (ZJU-UoE Institute),
Zhejiang University School of Medicine, Zhejiang University, Haining 314400, China.
Runhui Liu
State Key Laboratory of Bioreactor Engineering, Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering,
East China University of Science and Technology, Shanghai 200237, China.
Min Zhou
Department of Respiratory and Critical Care Medicine, the Fourth Affiliated Hospital,
Zhejiang University School of Medicine, Yiwu 223300, China.
Host defense peptides (HDPs) are one of the potentially promising agents for infection diseases due to their broad spectrum and low resistance rate, but their clinical applications are limited by proteolytic instability, high-cost, and complicated synthesis process. Here, we report a host-defense-peptide-mimicking β-peptide polymer that resists proteolysis to have enhanced the activity under physiological conditions, excellent antimicrobial efficiency even at high density of bacteria, and low cost for preparation. The β-peptide polymer demonstrated quorum sensing (QS) interference and bactericidal effect against both bacterial communities and individual bacterium to simultaneously block bacterial communication and disrupt bacterial membranes. The hierarchical QS network was suppressed, and main QS signaling systems showed considerably down-regulated gene expression, resulting in excellent biofilm eradication and virulence reduction effects. The dual-modal antibacterial ability possessed excellent therapeutic effects in Pseudomonas aeruginosa pneumonia, which could inhibit biofilm formation and exhibit better antibacterial and anti-inflammatory efficiency than clinically used antibiotics, levofloxacin. Furthermore, the β-peptide polymer also showed excellent therapeutic effect Escherichia coli pyogenic liver abscess. Together, we believed that the β-peptide polymer had a feasible clinical potential to treat bacterial infection diseases.
