Antimicrobial Activities of Dictyostelium Differentiation-Inducing Factors and Their Derivatives
Antimicrobial Activities of Dictyostelium Differentiation-Inducing Factors and Their Derivatives
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DOI：
10.3390/biom9050163
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发表时间：
2019-05-01
期刊：
影响因子：
5.5
通讯作者：
Kikuchi, Haruhisa
中科院分区：
文献类型：
--
作者：
Kubohara, Yuzuru;Shiratsuchi, Yoshiko;Kikuchi, Haruhisa
在其生命周期结束时，细胞粘菌盘基网柄菌形成由孢子和多细胞柄组成的子实体。最初，氯化烷基苯酮分化诱导因子 (DIF) -1 和 -3 是在盘状 D. 中作为茎细胞诱导剂分离出来的。后来，DIF 及其衍生物被证明具有多种生物活性，包括抗肿瘤和抗锥虫特性。在这项研究中，我们通过使用几种细菌物种检查了大约 30 种 DIF 衍生物的抗菌活性。几种 DIF 衍生物在亚微摩尔至低微摩尔范围的最低抑制浓度 (MIC) 下强烈抑制革兰氏阳性菌金黄色葡萄球菌、枯草芽孢杆菌、粪肠球菌和屎肠球菌的生长。相比之下，所评估的 DIF 衍生物对革兰氏阴性细菌大肠杆菌（MIC，>100 mu M）的生长没有任何显着影响。最重要的是，几种 DIF 衍生物强烈抑制耐甲氧西林金黄色葡萄球菌和耐万古霉素粪肠球菌和屎肠球菌的生长。透射电子显微镜显示，用 DIF 衍生物处理导致金黄色葡萄球菌中形成由细胞壁或质膜组成的独特多层结构。目前的结果表明，DIF 衍生物是开发新型抗菌药物的良好先导化合物。
At the end of its life cycle, the cellular slime mold Dictyostelium discoideum forms a fruiting body consisting of spores and a multicellular stalk. Originally, the chlorinated alkylphenone differentiation-inducing factors (DIFs) -1 and -3 were isolated as stalk cell inducers in D. discoideum. Later, DIFs and their derivatives were shown to possess several biologic activities including antitumor and anti-Trypanosoma properties. In this study, we examined the antibacterial activities of approximately 30 DIF derivatives by using several bacterial species. Several of the DIF derivatives strongly suppressed the growth of the Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, and Enterococcus faecalis and Enterococcus faecium, at minimum inhibitory concentrations (MICs) in the sub-micromolar to low-micromolar range. In contrast, none of the DIF derivatives evaluated had any noteworthy effect on the growth of the Gram-negative bacterium Escherichia coli (MIC, >100 mu M). Most importantly, several of the DIF derivatives strongly inhibited the growth of methicillin-resistant S. aureus and vancomycin-resistant E. faecalis and E. faecium. Transmission electron microscopy revealed that treatment with DIF derivatives led to the formation of distinct multilayered structures consisting of cell wall or plasma membrane in S. aureus. The present results suggest that DIF derivatives are good lead compounds for developing novel antimicrobials.