Department of Critical Care Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Department of School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, China.
Microbiol Spectr. 2024 Nov 5;12(11):e0026524. doi: 10.1128/spectrum.00265-24. Epub 2024 Oct 9.
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 demonstrated a rapid and effective sterilization against methicillin-resistant (MRSA), displaying both a minimum inhibitory concentration and a minimum bactericidal concentration of 8 µM. Mechanistic studies revealed that AMP W killed bacterial cells by disrupting the cytoplasmic membrane integrity, triggering leakage of cell contents. AMP W also exhibited excellent biocompatibility in both and safety evaluations. AMP W 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.
Increasing antibiotic resistance and the paucity of effective antibiotics necessitate innovative antibacterial agents. Methicillin-resistant (MRSA) is a major pathogen causing bacterial infections with high incidence and mortality rates, showing increasing resistance to clinical drugs. Antimicrobial peptides (AMPs) exhibit significant potential as alternatives to traditional antibiotics. This study designed a novel series of AMPs, characterized by a glycine-serine-glycine-centered symmetrical structure, and our results indicated that AMP W5 exhibited a rapid and effective bactericidal effect against MRSA. AMP W5 also demonstrated excellent biocompatibility and a bactericidal mechanism that disrupted membrane integrity, leading to leakage of cellular contents. The notable reduction in skin bacterial load observed in mouse models reinforced the clinical applicability of AMP W5. This study provides a promising solution for addressing the increasing threat of antibiotic-resistant bacteria and heralds new prospects for clinical applications.
抗生素耐药性在全球范围内构成重大公共卫生威胁。抗生素耐药性的上升和有效抗生素的急剧减少，需要开发创新的抗菌剂。基于甘氨酸-丝氨酸-甘氨酸的中心对称结构，结合色氨酸和精氨酸，我们设计了一系列具有广谱抗菌活性的抗菌肽 (AMP)。值得注意的是，AMP W 对耐甲氧西林金黄色葡萄球菌 (MRSA) 表现出快速而有效的杀菌作用，其最小抑菌浓度和最小杀菌浓度均为 8 µM。机制研究表明，AMP W 通过破坏细胞质膜完整性杀死细菌细胞，导致细胞内容物泄漏。AMP W 在 和 安全性评估中也表现出良好的生物相容性。AMP W 处理显著降低了我们的小鼠皮肤感染模型中的皮肤细菌负荷。总之，我们设计了一种新型的中心对称 AMP，代表了一种有前途的替代传统抗生素的医学方法，可用于治疗 MRSA 感染。
抗生素耐药性的增加和有效抗生素的缺乏需要创新的抗菌剂。耐甲氧西林金黄色葡萄球菌 (MRSA) 是一种主要的病原体，导致细菌感染的发病率和死亡率很高，对临床药物的耐药性不断增加。抗菌肽 (AMP) 作为传统抗生素的替代品具有巨大的潜力。本研究设计了一系列新型 AMP，其特征是具有甘氨酸-丝氨酸-甘氨酸为中心的对称结构，我们的结果表明 AMP W5 对 MRSA 具有快速有效的杀菌作用。AMP W5 还表现出良好的生物相容性和杀菌机制，破坏膜完整性，导致细胞内容物泄漏。在小鼠模型中观察到皮肤细菌负荷的显著减少，增强了 AMP W5 的临床适用性。这项研究为应对日益严重的抗生素耐药菌威胁提供了一个有前途的解决方案，并为临床应用开辟了新的前景。
