抗生素耐药性对全球公共卫生构成严重威胁，降低了传统抗生素治疗细菌感染的有效性。 ESKAPE 病原体是一组高度传播的细菌，主要促进抗生素耐药性的传播，并导致人类显着发病和死亡。 Phylloseptins 是一类源自叶蛙科青蛙的抗菌肽 (AMP)，已被证明通过膜相互作用具有抗菌活性。然而，它们相对较高的细胞毒性和较低的稳定性限制了这些AMP的临床开发。该项目旨在研究叶绿素类肽叶绿素-TO2（PSTO2）经过合理的氨基酸修饰后的抗菌活性和机制。在这里，从 Phyllomedusa tomopterna 的皮肤分泌物中鉴定出的 PSTO2 (FLSLIPHAISAVSALAKHL-NH2) 被用作修饰模板以增强抗菌活性。通过用 L-赖氨酸取代为 PSTO2 添加正电荷，增强了肽与细胞膜的相互作用，并提高了其抗菌功效。含有 D-赖氨酸的类似物 SRD7 和 SR2D10 对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌 (MRSA) 表现出显着的抗菌作用，同时还表现出降低的溶血活性和细胞毒性，从而产生更高的治疗指数。此外，用 D-赖氨酸修饰的 SRD7 对人类肺癌细胞系（包括 H838 和 H460）表现出显着的抗增殖特性。因此，这项研究为对抗抗生素耐药性的新型抗菌和抗癌药物提供了潜在的开发模型。

Antibiotic resistance poses a serious threat to public health globally, reducing the effectiveness of conventional antibiotics in treating bacterial infections. ESKAPE pathogens are a group of highly transmissible bacteria that mainly contribute to the spread of antibiotic resistance and cause significant morbidity and mortality in humans. Phylloseptins, a class of antimicrobial peptides (AMPs) derived from Phyllomedusidae frogs, have been proven to have antimicrobial activity via membrane interaction. However, their relatively high cytotoxicity and low stability limit the clinical development of these AMPs. This project aims to study the antimicrobial activity and mechanisms of a phylloseptin-like peptide, phylloseptin-TO2 (PSTO2), following rational amino acid modification. Here, PSTO2 (FLSLIPHAISAVSALAKHL-NH2), identified from the skin secretion of Phyllomedusa tomopterna, was used as the template for modification to enhance antimicrobial activity. Adding positive charges to PSTO2 through substitution with L-lysines enhanced the interaction of the peptides with cell membranes and improved their antimicrobial efficacy. The analogues SRD7 and SR2D10, which incorporated D-lysines, demonstrated significant antimicrobial effects against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) while also showing reduced haemolytic activity and cytotoxicity, resulting in a higher therapeutic index. Additionally, SRD7, modified with D-lysines, exhibited notable anti-proliferative properties against human lung cancer cell lines, including H838 and H460. This study thus provides a potential development model for new antibacterial and anti-cancer drugs combating antibiotic resistance.