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氨基酸修饰的共轭寡聚物自组装水凝胶用于高效捕获和特异性杀伤抗生素耐药菌。

Amino Acid-Modified Conjugated Oligomer Self-Assembly Hydrogel for Efficient Capture and Specific Killing of Antibiotic-Resistant Bacteria.

机构信息

Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering , Shaanxi Normal University , Xi'an 710062 , P. R. China.

出版信息

ACS Appl Mater Interfaces. 2019 May 8;11(18):16320-16327. doi: 10.1021/acsami.9b02643. Epub 2019 Apr 24.

Abstract

Bacterial infection is one of main causes that threaten global human health. Especially, antibiotic-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA) lead to high mortality rate and more expensive treatment cost. Here, a novel amino-acid-modified conjugated oligomer OTE-d-Phe was synthesized by modifying the side chain of conjugated oligo(thiophene ethynylene) with d-phenylalanine. By mixing 9-fluorenylmethyloxycarbonyl-l-phenylalanin (Fmoc-l-Phe) with OTE-d-Phe, a new and biocompatible low-molecular weight hydrogel (HG-2) was prepared through self-assembly. In solution, HG-2 can effectively capture bacteria spontaneously, such as Escherichia coli and MRSA. Most importantly, the hydrogel has specific and strong antibacterial activity against MRSA over methicillin-susceptible S. aureus, Staphylococcus epidermidis, and E. coli. Interestingly, when the hydrogel was put on a model surface, a piece of cloth, it also is able to selectively kill MRSA with low cell cytotoxicity. The antibacterial mechanism was investigated, and it demonstrated that the HG-2 interacts with and physically breaks the cell wall and membrane, which leads to MRSA death. Therefore, this new conjugated oligomer-based hydrogel provides promising applications in disinfection and therapy of MRSA in hospital and in community.

摘要

细菌感染是威胁全球人类健康的主要原因之一。特别是像耐甲氧西林金黄色葡萄球菌(MRSA)这样的抗生素耐药菌,导致高死亡率和更高的治疗成本。在这里,通过修饰共轭寡聚噻吩乙炔的侧链,合成了一种新型的氨基酸修饰的共轭寡聚物 OTE-d-Phe。通过将 9-芴甲氧羰基-l-苯丙氨酸(Fmoc-l-Phe)与 OTE-d-Phe 混合,通过自组装制备了一种新的、生物相容性的低分子量水凝胶(HG-2)。在溶液中,HG-2 可以自发有效地捕获细菌,如大肠杆菌和 MRSA。最重要的是,水凝胶对 MRSA 具有特异性和强抗菌活性,而对甲氧西林敏感的金黄色葡萄球菌、表皮葡萄球菌和大肠杆菌则没有活性。有趣的是,当水凝胶放在模型表面,如一块布上时,它也能够选择性地杀死 MRSA,同时细胞毒性很低。研究了其抗菌机制,表明 HG-2 与细胞壁和细胞膜相互作用并物理破坏它们,导致 MRSA 死亡。因此,这种基于新型共轭寡聚物的水凝胶为医院和社区中 MRSA 的消毒和治疗提供了有前途的应用。

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