Amine skeleton-based c-di-GMP derivatives as biofilm formation inhibitors
Amine skeleton-based c-di-GMP derivatives as biofilm formation inhibitors
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DOI：
10.1016/j.bmcl.2020.127713
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发表时间：
2021-01-15
影响因子：
2.7
通讯作者：
Demizu, Yosuke
中科院分区：
文献类型：
--
作者：
Ikeda, Kentaro;Yanase, Yuta;Demizu, Yosuke
细菌可以形成由多种细菌微生物组成的生物膜，作为抵御抗生素和宿主免疫系统等威胁的屏障。生物膜的形成显著地削弱了抗生素对致病菌的作用。抗生素的过度使用加速了多重耐药细菌（如耐甲氧西林金黄色葡萄球菌，MRSA）的出现，也是一个亟待解决的严重问题。因此，使用生物膜抑制剂作为一种治疗细菌感染相关疾病的新策略引起了人们的极大兴趣。从对细菌细胞作用方式的不同来看，生物膜抑制剂有望避免多重耐药细菌的出现。在这项研究中，我们开发了c-di-GMP的衍生物，c-di-GMP是一种环二核苷酸，有望具有抑制细菌生物膜形成的作用。一些合成的衍生物被发现能抑制革兰氏阳性菌的生物膜形成。
Bacteria can form a biofilm composed of diverse bacterial microorganism, which work as a barrier to protect from threats, such as antibiotics and host immunity system. The formation of biofilms significantly impairs the efficacy of antibiotics against pathogenic bacteria. It is also a serious problem to be solved that the emergence of multidrug-resistant bacteria (such as methicillin-resistant Staphylococcus aureus, MRSA) accelerated by the overuse of antibiotics. Therefore, the usage of biofilm inhibition agents has attracted immense interest as a novel strategy for treatment of diseases related to bacterial infection. From the difference of mode of action against bacterial cells, biofilm inhibition agents are expected to circumvent the emergence of multidrug-resistant bacteria. In this study, we have developed the derivatives of c-di-GMP, a kind of cyclic dinucleotide that is expected to have the effect of inhibiting bacterial biofilm formation. Some of the synthesized derivatives were found to inhibit biofilm formation of Gram-positive bacteria.