He Fangli, Liu Xi, Yang Sihui, Tan Huaxin, Yang Liu-Pan, Wang Li-Li
Department of Biochemistry and Molecular Biology, Laboratory of Nuclear Radiation DNA Damage and Repair, School of Basic Medicine, Hengyang Medical School, University of South China, Hengyang 421001, China.
School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang 421001, China.
ACS Appl Mater Interfaces. 2024 Dec 4;16(48):65955-65969. doi: 10.1021/acsami.4c16813. Epub 2024 Nov 19.
The rise of multidrug-resistant (MDR) bacteria poses a substantial challenge in clinical settings, particularly with the increasing prevalence of ESKAPE pathogens (, , , , , and ) as critical MDR bacteria. These ESKAPE pathogens have the capability to undermine antibiotic treatments, leading to a high incidence of drug resistance. However, the development of efficient antibacterial agents against ESKAPE pathogens is still in the bottleneck. Herein, the first example of antibacterial carbon dots against ESKAPE pathogens was reported. Onion powder-based carbon dots were melted with poly(hexamethylene biguanide) hydrochloride (PHMB) to obtain guanidinium-functionalized carbon dots (GCDs), which exhibited satisfactory antibacterial activity against all the tested bacteria, including both Gram-positive and Gram-negative bacteria, and even ESKAPE pathogens. The efficient antibacterial ability of GCDs derives from the rupture of the bacterial cell membrane and elevated ROS levels. Safety assessments revealed that GCDs neither trigger detectable drug resistance nor exhibit any cytotoxic effects. Furthermore, GCDs effectively promoted wound healing without observable adverse reactions of mixed MDR bacteria-infected wounds in rats. The GCDs also showed excellent long-term stability. These findings indicate that GCDs hold promise as an efficient antibacterial agent for the treatment of MDR strain-caused clinical infected-wound healing.
多重耐药（MDR）细菌的出现给临床环境带来了巨大挑战，尤其是随着ESKAPE病原体（粪肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和阴沟肠杆菌）作为关键的多重耐药细菌的患病率不断上升。这些ESKAPE病原体有能力破坏抗生素治疗，导致耐药性高发。然而，针对ESKAPE病原体的高效抗菌剂的开发仍处于瓶颈阶段。在此，报道了首例针对ESKAPE病原体的抗菌碳点。以洋葱粉为基础的碳点与聚（六亚甲基双胍）盐酸盐（PHMB）熔融，得到胍基功能化碳点（GCDs），其对所有测试细菌，包括革兰氏阳性菌和革兰氏阴性菌，甚至ESKAPE病原体都表现出令人满意的抗菌活性。GCDs的高效抗菌能力源于细菌细胞膜的破裂和活性氧水平的升高。安全性评估表明，GCDs既不会引发可检测到的耐药性，也不会表现出任何细胞毒性作用。此外，GCDs有效地促进了伤口愈合，对大鼠混合多重耐药细菌感染的伤口没有观察到不良反应。GCDs还表现出优异的长期稳定性。这些发现表明，GCDs有望成为一种治疗多重耐药菌株引起的临床感染伤口愈合的高效抗菌剂。
