Qi Guobin, Liu Xianglong, Li Hao, Qian Yunyun, Liu Can, Zhuang Jiahao, Shi Leilei, Liu Bin
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
Joint School of the National University of Singapore and Tianjin University, International Campus of Tianjin University, Binhai New City, Fuzhou 350207, China.
Sci Adv. 2025 Apr 11;11(15):eadp9448. doi: 10.1126/sciadv.adp9448.
Because of the rapid emergence of antibiotic-resistant bacteria, there is a growing need to discover antibacterial agents. Here, we design and synthesize a compound of TPA2PyBu that kills both Gram-negative and Gram-positive bacteria with an undetectably low drug resistance. Comprehensive analyses reveal that the antimicrobial activity of TPA2PyBu proceeds via a unique dual mechanism by damaging bacterial membrane integrity and inducing DNA aggregation. TPA2PyBu could provide imaging specificity that differentiates bacterial infection from inflammation and cancer. High in vivo treatment efficacy of TPA2PyBu was achieved in methicillin-resistant infection mouse models. This promising antimicrobial agent suggests that combining multiple mechanisms of action into a single molecule can be an effective approach to address challenging bacterial infections.
由于抗生素耐药菌的迅速出现，发现抗菌剂的需求日益增长。在此，我们设计并合成了一种化合物TPA2PyBu，它能杀死革兰氏阴性菌和革兰氏阳性菌，且耐药性低到难以检测。综合分析表明，TPA2PyBu的抗菌活性通过一种独特的双重机制发挥作用，即破坏细菌膜的完整性并诱导DNA聚集。TPA2PyBu能够提供成像特异性，以区分细菌感染与炎症及癌症。在耐甲氧西林感染小鼠模型中，TPA2PyBu在体内显示出高治疗效果。这种有前景的抗菌剂表明，将多种作用机制整合到一个分子中可能是应对具有挑战性的细菌感染的有效方法。
