Antimicrobial activity of novel symmetrical antimicrobial peptides centered on a hydrophilic motif against resistant clinical isolates: in vitro and in vivo analyses

作者：Chaoqun Zhang, Le Fu, Yuan Zhu, Qigui Chen, Zetong Chen, Yung‐Fu Chang, Yide Li, Mengjing Yao, Xinyi Huang, Jin Li, Xueqin Gao, Yiyu Zhang, Biao Jin, Shuli Chou, Liang Luo · 发表于：Microbiology Spectrum · 年份：2024 · DOI：10.1128/spectrum.00265-24 · 被引用次数：6 · 研究领域：Antimicrobial Peptides and Activities、Biochemical and Structural Characterization、Antimicrobial agents and applications

ABSTRACT Antibiotic resistance poses a significant public health threat worldwide. The rise in antibiotic resistance and the sharp decline in effective antibiotics necessitate the development of innovative antibacterial agents. Based on the central symmetric structure of glycine–serine–glycine, combined with tryptophan and arginine, we designed a range of antimicrobial peptides (AMPs) that exhibited broad-spectrum antibacterial activity. Notably, AMP W 5 demonstrated a rapid and effective sterilization against methicillin-resistant Staphylococcus aureus (MRSA), displaying both a minimum inhibitory concentration and a minimum bactericidal concentration of 8 µM. Mechanistic studies revealed that AMP W 5 killed bacterial cells by disrupting the cytoplasmic membrane integrity, triggering leakage of cell contents. AMP W 5 also exhibited excellent biocompatibility in both in vitro and in vivo safety evaluations. AMP W 5 treatment significantly reduced skin bacterial load in our murine skin infection model. In conclusion, we designed a novel centrosymmetric AMP representing a promising medical alternative to conventional antibiotics for treating MRSA infections. IMPORTANCE Increasing antibiotic resistance and the paucity of effective antibiotics necessitate innovative antibacterial agents. Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing bacterial infections with high incidence and mortality rates, showing increasing resistance to clinical drugs. Antimi...