Chen Xueyan, Song Meirong, Tian Lei, Shan Xinxin, Mao Changsi, Chen Minghui, Zhao Jiaqi, Sami Abdul, Yin Haoqiang, Ali Usman, Shi Jiawei, Li Hehuan, Zhang Yuqian, Zhang Jinghua, Wang Shunxi, Shi Chun-Lin, Chen Yanhui, Du Xiang-Dang, Zhu Kui, Wu Liuji
State Key Laboratory of High-Efficiency Production of Wheat-Maize Double Cropping, Center for Crop Genome Engineering, College of Agronomy, Henan Agricultural University, Zhengzhou 450046, China.
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Sci Adv. 2025 Mar 21;11(12):eadt8239. doi: 10.1126/sciadv.adt8239. Epub 2025 Mar 19.
Multidrug-resistant (MDR) bacteria pose a major threat to public health, and additional sources of antibacterial candidates are urgently needed. Noncanonical peptides (NCPs), derived from noncanonical small open reading frames, represent small biological molecules with important roles in biology. However, the antibacterial activity of NCPs remains largely unknown. Here, we discovered a plant-derived noncanonical antibacterial peptide (NCBP1) against both Gram-positive and Gram-negative bacteria. NCBP1 is composed of 11 amino acid residues with cationic surface potential and favorable safety and stability. Mechanistic studies revealed that NCBP1 displayed antibacterial activity by targeting phosphatidylglycerol and cardiolipin in bacterial membrane, resulting in membrane damage and dysfunction. Notably, NCBP1 showed promising efficacy in mice. Furthermore, NCBP1 effectively inhibited the growth of plant fungal pathogens and enhanced disease resistance in maize. Our results demonstrate the unexplored antimicrobial potential of plant-derived NCPs and provide an accessible source for the discovery of antimicrobial substances against MDR bacterial and fungal pathogens.
多重耐药（MDR）细菌对公共卫生构成重大威胁，因此迫切需要寻找新的抗菌候选物来源。非经典肽（NCPs）源自非经典小开放阅读框，是一类在生物学中具有重要作用的小生物分子。然而，NCPs的抗菌活性在很大程度上仍不为人知。在此，我们发现了一种源自植物的对革兰氏阳性菌和革兰氏阴性菌均有效的非经典抗菌肽（NCBP1）。NCBP1由11个氨基酸残基组成，具有阳离子表面电位，安全性和稳定性良好。机制研究表明，NCBP1通过靶向细菌膜中的磷脂酰甘油和心磷脂发挥抗菌活性，导致膜损伤和功能障碍。值得注意的是，NCBP1在小鼠实验中显示出良好的疗效。此外，NCBP1能有效抑制植物真菌病原体的生长，并增强玉米的抗病能力。我们的研究结果揭示了植物源NCPs尚未被发掘的抗菌潜力，并为发现针对多重耐药细菌和真菌病原体的抗菌物质提供了一个可利用的来源。
