Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, P. R. China.
Adv Sci (Weinh). 2024 Aug;11(30):e2401793. doi: 10.1002/advs.202401793. Epub 2024 Jun 14.
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.
抗生素耐药性的兴起构成了重大的公共健康危机，特别是由于治疗革兰氏阴性病原体感染的抗菌选择有限。在这里，我们描述了一种抗菌肽（AMP）SR25，它通过独特的双重靶向机制有效杀死革兰氏阴性和革兰氏阳性细菌，而没有检测到耐药性。同时，开发了一种基于 SR25 的水凝胶用于有效治疗感染性糖尿病伤口。SR25 通过从一种未培养的牛肠放线菌 Nonomuraea Jilinensis sp. nov. 的基因组挖掘获得。研究表明，SR25 有两个独立的细胞靶标，破坏细菌膜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，含有 SR25 的水凝胶对大肠杆菌（E. coli）和耐甲氧西林金黄色葡萄球菌（MRSA）混合感染具有很高的疗效，加速了伤口愈合。总的来说，这些发现表明了 SR25 的治疗潜力，并强调了从未培养的动物共生菌中挖掘具有多种机制的药物来对抗具有挑战性的细菌病原体的价值。
