A polymeric approach toward resistance-resistant antimicrobial agent with dual-selective mechanisms of action.
A polymeric approach toward resistance-resistant antimicrobial agent with dual-selective mechanisms of action.
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具有双重选择性作用机制的抗耐药性抗菌剂的聚合方法
DOI：
10.1126/sciadv.abc9917
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发表时间：
2021-01
期刊：
影响因子：
13.6
通讯作者：
Feng X
中科院分区：
文献类型：
--
作者：
Bai S;Wang J;Yang K;Zhou C;Xu Y;Song J;Gu Y;Chen Z;Wang M;Shoen C;Andrade B;Cynamon M;Zhou K;Wang H;Cai Q;Oldfield E;Zimmerman SC;Bai Y;Feng X
具有两种细菌特异性作用机制的寡聚脒显示出广谱、抗耐药性的抗菌作用。抗生素耐药性现在是人类健康的主要威胁，应对这一威胁的方法之一是开发耐药性抗生素。合成抗菌聚合物通常具有抗耐药性，活性良好，耐药率低，但治疗指数通常较低。在这里，我们通过向富含脒的短聚合物引入双重选择性作用机制来解决这个问题，该聚合物可以同时破坏细菌膜并与细菌 DNA 结合。寡聚脒显示出不可观察到的耐药性产生，但针对许多细菌类型具有高治疗指数，例如对多种药物（包括粘菌素）耐药的 ESKAPE 菌株和临床分离株。该寡聚物在各种模型系统中表现出优异的有效性，在哺乳动物细胞存在的情况下杀死细胞外或细胞内细菌，去除秀丽隐杆线虫的所有细菌，并拯救严重感染的小鼠。这种“双重作用机制”方法可能是抗菌聚合物未来发展的总体策略。
An oligoamidine with two bacteria-specific mechanisms of action showed broad-spectrum, resistance-resistant antimicrobial effect. Antibiotic resistance is now a major threat to human health, and one approach to combating this threat is to develop resistance-resistant antibiotics. Synthetic antimicrobial polymers are generally resistance resistant, having good activity with low resistance rates but usually with low therapeutic indices. Here, we report our solution to this problem by introducing dual-selective mechanisms of action to a short amidine-rich polymer, which can simultaneously disrupt bacterial membranes and bind to bacterial DNA. The oligoamidine shows unobservable resistance generation but high therapeutic indices against many bacterial types, such as ESKAPE strains and clinical isolates resistant to multiple drugs, including colistin. The oligomer exhibited excellent effectiveness in various model systems, killing extracellular or intracellular bacteria in the presence of mammalian cells, removing all bacteria from Caenorhabditis elegans, and rescuing mice with severe infections. This “dual mechanisms of action” approach may be a general strategy for future development of antimicrobial polymers.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
DOI：
10.1016/j.bbapap.2008.11.005
发表时间：
2009-05
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
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通讯作者：
Delcour AH
影响因子：
64.5
作者：
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通讯作者：
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影响因子：
14.9
作者：
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通讯作者：
Portugal, J
影响因子：
5.2
作者：
Kamaruzzaman, Nor Fadhilah;Firdessa, Rebuma;Good, Liam
通讯作者：
Good, Liam