21:T457,The emergence of multidrug-resistant bacteria has dramatically increased the lethality, level of resistance, and difficulty of treatment. In this study, a series of new antimicrobial peptides (AMPs) based on the β-hairpin structure with the template (XY)₂RRRF(YX)₂-NH₂ (X: hydrophobic amino acids; Y: cationic amino acids) were synthesized; surprisingly, almost all of the new peptides have strong antibacterial activity and negligible hemolytic toxicity. Particularly, the therapeutic index (TI) values of F(RI)2R and F(KW)2K reached up to 115.9 and 70.7, respectively. In addition, they did not show induced drug resistance and inhibited the development of antibiotic resistance when combined and used with traditional antibiotics. In addition, their antibacterial mechanism was preliminarily studied. Moreover, the new peptides F(RI)2R and F(KW)2K showed excellent performance in the pulmonary bacterial infection model and low toxicity in mice. In conclusion, F(RI)2R and F(KW)2K are considered new antimicrobial alternatives to address the antimicrobial-resistance crisis.22:T48f,Nonselective toxicity of antimicrobial peptides (AMPs) needs to be solved urgently for their application. Temporin-PE (T-PE, FLPIVAKLLSGLL-NH₂), an AMP extracted from skin secretions of frogs, has high toxicity and specific antimicrobial activity against Gram-positive bacteria. To improve the antimicrobial performance of T-PE, a series of T-PE analogues were designed and synthesized by glutamic acid full-scan, and then their key positions were replaced with lysine. Finally, E₁₁K₄K₁₀, the highest therapeutic indicial AMP, was screened out. E₁₁K₄K₁₀ was not easy to induce and produce drug-resistant bacteria when used alone, as well as it could also inhibit the development of the drug resistance of traditional antibiotics when it was used in combination with the traditional antibiotics. In addition, E₁₁K₄K₁₀ had an excellent therapeutic effect on a mouse model of pulmonary bacterial infection. Taken together, this study provides a new approach for the further improvement of new antimicrobial peptides against the antimicrobial-resistance crisis.23:T473,Antimicrobial peptides (AMPs) have emerged as promising agents to combat the antibiotic resistance crisis due to their rapid bactericidal activity and low propensity for drug resistance. However, AMPs face challenges in terms of balancing enhanced antimicrobial efficacy with increased toxicity during modification processes. In this study, de novo d-type β-hairpin AMPs are designed. The conformational transformation of self-assembling peptide W-4 in the environment of the bacterial membrane and the erythrocyte membrane affected its antibacterial activity and hemolytic activity and finally showed a high antibacterial effect and low toxicity. Furthermore, W-4 displays remarkable stability, minimal occurrence of drug resistance, and synergistic effects when combined with antibiotics. The in vivo studies confirm its high safety and potent wound-healing properties at the sites infected by bacteria. This study substantiates that nanostructured AMPs possess enhanced biocompatibility. These advances reveal the superiority of self-assembled AMPs and contribute to the development of nanoantibacterial materials.24:T4fe,Developing a straightforward and effective strategy to modify antimicrobial peptides (AMPs) is crucial in overcoming the challenges posed by their instability and toxicity. Phosphorylation can reduce toxicity and improve the stability of AMPs. Based on these, we designed a series of peptides and their corresponding phosphorylated forms. The results showed that all phosphorylated peptides displayed reduced toxicity and enhanced stability compared to their unphosphorylated counterparts. Among them, W₃BipY₈-P stood out as the most promising peptide, exhibiting similar antibacterial activity as its unphosphorylated analog

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