Violacein Targets the Cytoplasmic Membrane of Bacteria
Violacein Targets the Cytoplasmic Membrane of Bacteria
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DOI：
10.1021/acsinfecdis.8b00245
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发表时间：
2019-04-01
影响因子：
5.3
通讯作者：
Gueiros-Filho, Frederico J.
中科院分区：
文献类型：
--
作者：
Cauz, Ana C. G.;Carretero, Gustavo P. B.;Gueiros-Filho, Frederico J.
紫罗兰素是一种由环境细菌产生的色氨酸衍生的紫色色素，具有多种生物活性，包括对革兰氏阳性病原体的强烈抑制作用。在这里，我们采用组合实验方法来确定紫罗兰素杀死革兰氏阳性细菌的机制。荧光显微镜观察显示，紫色素快速和显着渗透B。subtilis和S.金黄色葡萄球菌细胞细胞透化伴随着细胞质膜中可见的不连续或裂缝的出现，但它不影响细胞壁。使用体外实验，我们表明，紫花苜蓿素直接结合到脂质体与商业和细菌磷脂和扰乱他们的结构和渗透性。此外，分子动力学模拟，揭示了如何紫色插入到脂质双层。因此，我们的综合结果表明，细胞质膜是紫色菌素在细菌中的主要目标。讨论了这一发现对紫罗兰素作为治疗剂开发的影响。
Violacein is a tryptophan-derived purple pigment produced by environmental bacteria, which displays multiple biological activities, including strong inhibition of Gram-positive pathogens, Here, we applied a combination of experimental approaches to identify the mechanism by which violacein kills Gram-positive bacteria. Fluorescence microscopy showed that violacein quickly and dramatically permeabilizes B. subtilis and S. aureus cells. Cell permeabilization was accompanied by the appearance of visible discontinuities or rips in the cytoplasmic membrane, but it did not affect the cell wall. Using in vitro experiments, we showed that violacein binds directly to liposomes made with commercial and bacterial phospholipids and perturbs their structure and permeability. Furthermore, molecular dynamics simulations were employed to reveal how violacein inserts itself into lipid bilayers. Thus, our combined results demonstrate that the cytoplasmic membrane is the primary target of violacein in bacteria. The implications of this finding for the development of violacein as a therapeutic agent are discussed.