Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos #04-01, Singapore 138669, Singapore.
Biomater Sci. 2019 May 28;7(6):2317-2325. doi: 10.1039/c8bm01683f.
Antimicrobial resistance (AMR) has become a global public health threat. One of the major causes of AMR development is the accumulation of low levels of antimicrobials in the environment. To tackle this problem, novel antimicrobial agents that do not leave active residues after treatment are needed. In this study, a strategy for synthesizing a series of main-chain imidazolium oligomers that incorporate carbonate, hemiaminal, ester and urea functional groups to serve as degradable linkers is presented. These oligomers exhibit excellent microbicidal activity and kill E. coli at low concentrations in a short time (99% killing efficiency in 2 min). Moreover, the oligomers are self-degradable and biocompatible. The degradation of these oligomers is studied in buffered solutions with different pH. Under basic conditions (pH = 8), carbonate-linked and ester-linked oligomers degrade to inactive and less toxic small molecules within weeks, making it less likely for these oligomers to induce antimicrobial resistance as compared to traditional antibiotics. The application of these oligomers for the in vivo treatment of S. aureus infected wounds is demonstrated in a mouse model. Notably, the oligomers demonstrate antibacterial efficacy and accelerated wound healing comparable to vancomycin, a first-line antibiotic for the treatment of complicated skin infections.
抗微生物药物耐药性（AMR）已成为全球公共卫生威胁。AMR 发展的主要原因之一是环境中低水平的抗菌药物积累。为了解决这个问题，需要使用新型的抗菌药物，这些药物在治疗后不会留下活性残留。在这项研究中，提出了一种合成一系列包含碳酸酯、亚胺、酯和脲官能团的主链咪唑啉低聚物的策略，用作可降解的连接物。这些低聚物表现出优异的杀菌活性，能够在短时间内以低浓度杀死大肠杆菌（2 分钟内达到 99%的杀灭效率）。此外，这些低聚物具有自我降解性和生物相容性。在具有不同 pH 值的缓冲溶液中研究了这些低聚物的降解情况。在碱性条件下（pH = 8），碳酸酯连接和酯连接的低聚物在数周内降解为无活性和毒性较低的小分子，与传统抗生素相比，这些低聚物不太可能诱导抗微生物药物耐药性。在金黄色葡萄球菌感染伤口的小鼠模型中证明了这些低聚物的体内治疗应用。值得注意的是，这些低聚物表现出与万古霉素相当的抗菌功效和加速伤口愈合的效果，万古霉素是治疗复杂皮肤感染的一线抗生素。
