Innovative Enzyme-Resistant Nano-Antimicrobial Peptides Combat Drug-Resistant Bacterial Infections

Recently, the Active Peptide and Feed Innovation Research Team from the Institute of Feed Research, Chinese Academy of Agricultural Sciences developed a bacteria-responsive self-assembling antimicrobial peptide based on precise module design strategies. The relevant research findings have been published in the Journal of Nanobiotechnology .

The wide-spreading of multidrug resistance poses a significant threat to human and animal health. Antimicrobial peptides (AMPs) have garnered attention due to their high antimicrobial activity and low resistance. However, their susceptibility to enzymatic degradation in vivo is a bottleneck in their clinical application.

In this study, based on the precise module design strategies of self-assembled peptides and antibacterial structure function relationships, a bacterial-responsive self-assembly platform consisting of hydrophobic, hydrogen-bonding and antimicrobial modules were constructed and screened potent antimicrobial, highly stable and low-toxicity in situ self-assembled AMPs. The screened AMP self-assembled into nanoparticles in vitro and initiated nanoparticle-to-nanofiber conversion under the action of bacterial cell wall LTA or LPS nucleation sites, thereby achieving bacterial capture and further disrupting the cell membrane lipid bilayer arrangement of the bacterial cell membrane and causing bacterial death. In vivo mouse mastitis infection model further confirmed the therapeutic potential and promising biosafety of the self-assembled peptide, which can effectively alleviate mastitis caused by MDR Escherichia coli and Staphylococcus aureus , and eliminate pathogenic bacteria. Hence, the self-assembled AMPs have emerged as a viable and potent therapeutic intervention, exhibiting notable efficacy in both systemic and localized therapeutic strategies. The study provides new insights into the research of AMPs stabilization techniques and offers solutions for inhibiting multiple drug-resistant bacterial infections.

The research was supported by the National Key Research and Development Plan, the National Natural Science Foundation of China, and The Innovation Program of Agricultural Science and Technology (ASTIP) in Chinese Academy of Agricultural Sciences (CAAS) and its key projects.

Original link: https://doi.org/10.1186/s12951-024-02896-5

Source: Xuanxuan Ma, wangjianhua@caas.cn