Self-assembly of antimicrobial peptide nanofibers enhances enzymatic stability for dual-mode capture and killing of multidrug-resistant clinical isolates
文献类型： 外文期刊
作者： Ma, Xuanxuan 1 ; Mao, Ruoyu 1 ; Hao, Ya 1 ; Li, Yuanyuan 1 ; Li, Xuan 1 ; Teng, Da 1 ; Yang, Na 1 ; Wang, Jianhua 1 ;
作者机构： 1.Chinese Acad Agr Sci, Feed Res Inst, Gene Engn Lab, Innovat Team Antimicrobial Peptides & Alternat Ant, Beijing 100081, Peoples R China
2.China Agr Univ, State Key Lab Farm Anim Biotech Breeding, Beijing, Peoples R China
关键词： Antimicrobial peptides; Self-assembly; Nanofibers; Protease resistance; Bacterial entrapment
期刊名称：CHEMICAL ENGINEERING JOURNAL （ 影响因子：13.2； 五年影响因子：13.5 ）
ISSN： 1385-8947
年卷期： 2025 年 519 卷
页码：
收录情况： SCI
摘要： The global rise of multidrug-resistant (MDR) bacteria due to antibiotic overuse represents a critical public health emergency, demanding innovative antimicrobial solutions. This urgency is particularly acute for WHO-priority ESKAPE pathogens, including Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), which demonstrate alarming resistance rates in bovine mastitis and zoonotic transmission. While antimicrobial peptides (AMPs) offer promise against MDR pathogens, their clinical translation has been hindered by instability issues. Here, we present a supramolecular engineering strategy integrating a self-assembling core with an antimicrobial domain to construct chimeric AMPs KN that synergize membrane-disruptive mechanisms with nano-structural advantages. Molecular dynamics and fluorescence spectroscopy validated that KN self-assembled into nanofibers at a critical micelle concentration (CMC) of 72.73 mu M, demonstrating broad-spectrum antimicrobial activity (geometric mean MIC: 3.54 mu M) and exceptional biocompatibility (>90% cell viability). KN maintains robust antimicrobial performance under physiological stressors including serum exposure, and proteolytic environments (trypsin/hepato-renal tissues), demonstrating 1.2-fold enhanced enzymatic resistance than parent peptide. Mechanistic studies revealed that KN selectively bound to lipopolysaccharide (LPS) and lipoteichoic acid (LTA), accelerating dynamic nanofiber assembly to entrap pathogens and disrupt membrane integrity. In murine mastitis models induced by MDR E. coli CGMCC 1.90026 and S. aureus CGMCC 1.90032, KN treatment achieved 100% (E. coli) and 86.1% (S. aureus) bacterial clearance in mammary tissue, balanced inflammatory cytokines and restored blood-milk barrier integrity, thus confirming the therapeutic potential of KN. This modular domain design achieves concurrent optimization of structural stability and antimicrobial potency, establishing a transformative supramolecular blueprint against drug-resistant pathogens.
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