Cauz Ana C G, Carretero Gustavo P B, Saraiva Greice K V, Park Peter, Mortara Laura, Cuccovia Iolanda M, Brocchi Marcelo, Gueiros-Filho Frederico J
Departamento de Genética, Evolução, Microbiologia e Imunologia, Instituto de Biologia , Universidade Estadual de Campinas , Rua Monteiro Lobato 255 , Campinas , São Paulo 13083-862 , Brazil.
Departamento de Bioquímica, Instituto de Química , Universidade de São Paulo , Av. Professor Lineu Prestes 748 , São Paulo , São Paulo 05508-000 , Brazil.
ACS Infect Dis. 2019 Apr 12;5(4):539-549. doi: 10.1021/acsinfecdis.8b00245. Epub 2019 Feb 12.
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.
紫菌素是一种由环境细菌产生的源自色氨酸的紫色色素，它具有多种生物活性，包括对革兰氏阳性病原体的强烈抑制作用。在此，我们应用了多种实验方法来确定紫菌素杀死革兰氏阳性细菌的机制。荧光显微镜显示，紫菌素能迅速且显著地使枯草芽孢杆菌和金黄色葡萄球菌细胞通透性增加。细胞通透性增加伴随着细胞质膜出现可见的间断或裂口，但不影响细胞壁。通过体外实验，我们表明紫菌素直接与由商业和细菌磷脂制成的脂质体结合，并扰乱其结构和通透性。此外，利用分子动力学模拟来揭示紫菌素如何插入脂质双层。因此，我们的综合结果表明细胞质膜是紫菌素在细菌中的主要作用靶点。本文讨论了这一发现对将紫菌素开发为治疗剂的意义。
