Frontiers Science Center for Flexible Electronics, (FSCFE), Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering (IBME), Ningbo Institute, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, China.
Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo Cixi Institute of Biomedical Engineering, 1219 West Zhongguan Road, Ningbo 315201, China.
Sci Adv. 2024 Aug 30;10(35):eadp6604. doi: 10.1126/sciadv.adp6604. Epub 2024 Aug 28.
ESKAPE pathogens are a panel of most recalcitrant bacteria that could "escape" the treatment of antibiotics and exhibit high incidence of drug resistance. The emergence of multidrug-resistant (MDR) ESKAPE pathogens (particularly Gram-negative bacteria) accounts for high risk of mortality and increased resource utilization in health care. Worse still, there has been no new class of antibiotics approved for exterminating the Gram-negative bacteria for more than 50 years. Therefore, it is urgent to develop novel antibacterial agents with low resistance and potent killing efficacy against Gram-negative ESKAPE pathogens. Herein, we present a class of fluoropolymers by mimicking the amphiphilicity of cationic antimicrobial peptides. Our optimal fluoroamphiphilic polymer (PDHF) displayed selective antimicrobial ability for all MDR Gram-negative ESAKPE pathogens, low resistance, high in vitro cell selectivity, and in vivo curative efficacy. These findings implied great potential of fluoroamphiphilic cationic polymers as promising antibacterial agents against MDR Gram-negative ESKAPE bacteria and alleviating antibiotic resistance.
ESKAPE 病原体是一组最难治疗的细菌，它们可以“逃避”抗生素的治疗，并表现出很高的耐药性。多药耐药（MDR）ESKAPE 病原体（特别是革兰氏阴性菌）的出现导致了医疗保健中高死亡率和资源利用增加的风险。更糟糕的是，50 多年来，还没有批准用于消灭革兰氏阴性菌的新一类抗生素。因此，迫切需要开发具有低耐药性和针对革兰氏阴性 ESKAPE 病原体的强大杀伤功效的新型抗菌剂。本文通过模拟阳离子抗菌肽的两亲性，提出了一类氟聚合物。我们的最佳氟两亲聚合物（PDHF）对所有 MDR 革兰氏阴性 ESAKPE 病原体均表现出选择性抗菌能力、低耐药性、高体外细胞选择性和体内治疗效果。这些发现表明氟两亲阳离子聚合物作为有前途的抗 MDR 革兰氏阴性 ESKAPE 细菌的抗菌剂和缓解抗生素耐药性具有巨大的潜力。
