Abstract：
The rise of antibiotic resistance poses a significant public health crisis, particularly due to limited antimicrobial options for the treatment of infections with Gram-negative pathogens. Here, an antimicrobial peptide (AMP) SR25 is characterized, which effectively kills both Gram-negative and Gram-positive bacteria through a unique dual-targeting mechanism without detectable resistance. Meanwhile, an SR25-functionalized hydrogel is developed for the efficient treatment of infected diabetic wounds. SR25 is obtained through genome mining from an uncultured bovine enteric actinomycete named Nonomuraea Jilinensis sp. nov. Investigations reveal that SR25 has two independent cellular targets, disrupting bacterial membrane integrity and restraining the activity of succinate:quinone oxidoreductase (SQR). In a diabetic mice wound infection model, the SR25-incorporated hydrogel exhibits high efficacy against mixed infections of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), accelerating wound healing. Overall, these findings demonstrate the therapeutic potential of SR25 and highlight the value of mining drugs with multiple mechanisms from uncultured animal commensals for combating challenging bacterial pathogens.
摘要：
抗生素耐药性的上升带来了严重的公共卫生危机，特别是由于用于治疗革兰氏阴性病原体感染的抗菌选择有限。这里,抗菌肽（AMP）SR25的特征，其通过独特的双靶向机制有效地杀死革兰氏阴性和革兰氏阳性细菌而没有可检测的抗性。同时,SR25官能化的水凝胶被开发用于感染的糖尿病伤口的有效治疗。SR25是通过基因组挖掘从未培养的牛肠放线菌NonomuraeaJilinensissp。11月。研究表明，SR25具有两个独立的细胞靶标，破坏细菌膜的完整性并抑制琥珀酸：醌氧化还原酶（SQR）的活性。在糖尿病小鼠伤口感染模型中，掺入SR25的水凝胶对大肠杆菌的混合感染表现出很高的功效（E.大肠杆菌)和耐甲氧西林金黄色葡萄球菌(MRSA)，加速伤口愈合.总的来说,这些发现证明了SR25的治疗潜力,并突出了从未培养的动物共生体中挖掘具有多种机制的药物对对抗具有挑战性的细菌病原体的价值.
