Nature-inspired antimicrobial polymers--assessment of their potential for biomedical applications.
Nature-inspired antimicrobial polymers--assessment of their potential for biomedical applications.
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DOI：
10.1371/journal.pone.0073812
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lienkamp K
中科院分区：
文献类型：
--
作者：
Al-Ahmad A;Laird D;Zou P;Tomakidi P;Steinberg T;Lienkamp K
我们探索了基于聚氧冰片烯的抗菌肽(SMAMPs)的合成模拟物(SMAMPs)的潜力，SMAMPs是一类具有细胞选择性和低耐药性开发潜力的新型抗菌聚合物，具有临床应用前景。我们评估了它们对七种临床和监管相关细菌菌株的抗菌活性，并用两种不同的原代人类细胞测试了它们的毒性。抗菌活性测定采用最低抑菌浓度(MIC)法，并根据NCCLS标准确定最低杀菌浓度(MBC)。结果揭示了在测试两亲性阳离子聚合物的抗菌活性时可能出现的具体问题，并证实了我们产品组合中更亲水的SMAMP聚合物具有“双重选择性”的工作假设，即它们不仅对细菌比哺乳动物细胞有选择性，而且对革兰氏阳性菌比革兰氏阴性菌有选择性。数据还表明，我们可以提高一个SMAMP的宽带活性，并结合细胞毒性实验的结果，确定该聚合物是一个有希望的候选进一步的体外和体内测试。透射电子研究表明，SMAMP对细菌膜的作用使大肠杆菌和金黄色葡萄球菌的细胞膜受到严重破坏，这支持了SMAMP与抗菌肽非常相似的观点。为了测试细胞毒性，我们使用了传统的人红细胞溶血试验和原代人成纤维细胞的xCelligence试验。这里报告的数据是溶血试验以xCelligence试验为基准的第一个例子。它表明，使用这些互补的方法也可以获得相同的趋势。这建立了以原代人类细胞为基础的xCelligence分析，作为SMAMP表征的有用工具。
We explored the potential of poly(oxonorbornene)-based synthetic mimics of antimicrobial peptides (SMAMPs), a promising new class of antimicrobial polymers with cell-selectivity and low resistance development potential, for clinical applications. We evaluated their antimicrobial activity against a panel of seven clinical and regulatory relevant bacteria strains, and tested their toxicity with two different kinds of primary human cells. For the antimicrobial activity, we performed the minimum inhibitory concentration (MIC) assay and determined the minimum bactericidal concentration (MBC) according to the NCCLS guidelines. The results revealed specific problems that may occur when testing the antimicrobial activity of amphiphilic cationic polymers, and confirmed the working hypothesis that the more hydrophilic SMAMP polymers in our portfolio were ‘doubly selective’, i.e. they are not only selective for bacteria over mammalian cells, but also for Gram-positive over Gram-negative bacteria. The data also showed that we could improve the broad-band activity of one SMAMP, and in combination with the results from the cell toxicity experiments, identified this polymer as a promising candidate for further in-vitro and in-vivo testing. Transmission electron studies revealed that the cellular envelopes of both E. coli and S. aureus were severely damaged due to SMAMP action on the bacterial membrane, which strengthened the argument that SMAMPs closely resemble antimicrobial peptides. To test cell toxicity, we used the traditional hemolysis assay with human red blood cells, and the novel xCelligence assay with primary human fibroblasts. The data reported here is the first example in which a hemolysis assay is benchmarked against the xCelligence assay. It revealed that the same trends were obtained using these complementary methods. This establishes the xCelligence assay with primary human cells as a useful tool for SMAMP characterization.
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影响因子：
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