Here it is demonstrated how some anionic food additives commonly used in our diet, such as tartrazine (TZ), bind to DHVAR4, an antimicrobial peptide (AMP) derived from oral host defense peptides, resulting in significantly fostered toxic activity against both Gram-positive and Gram-negative bacteria, but not against mammalian cells. Biophysical studies on the DHVAR4–TZ interaction indicate that initially large, positively charged aggregates are formed, but in the presence of lipid bilayers, they rather associate with the membrane surface. In contrast to synergistic effects observed for mixed antibacterial compounds, this is a principally different mechanism, where TZ directly acts on the membrane-associated AMP promoting its biologically active helical conformation. Model vesicle studies show that compared to dye-free DHVAR4, peptide–TZ complexes are more prone to form H-bonds with the phosphate ester moiety of the bilayer head-group region resulting in more controlled bilayer fusion mechanism and concerted severe cell damage. AMPs are considered as promising compounds to combat formidable antibiotic-resistant bacterial infections; however, we know very little on their in vivo actions, especially on how they interact with other chemical agents. The current example illustrates how food dyes can modulate AMP activity, which is hoped to inspire improved therapies against microbial infections in the alimentary tract. Results also imply that the structure and function of natural AMPs could be manipulated by small compounds, which may also offer a new strategic concept for the future design of peptide-based antimicrobials.

中文翻译：

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阴离子食品色素柠檬黄通过微调其膜活性来增强组蛋白衍生肽 DHVAR4 的抗菌功效

这里展示了我们饮食中常用的一些阴离子食品添加剂，如柠檬黄 (TZ)，如何与 DHVAR4 结合，DHVAR4 是一种源自口腔宿主防御肽的抗菌肽 (AMP)，从而显着增强了对革兰氏阳性菌的毒性活性和革兰氏阴性菌，但不针对哺乳动物细胞。对 DHVAR4-TZ 相互作用的生物物理研究表明，最初形成了带正电的大聚集体，但在脂质双层存在的情况下，它们与膜表面结合。与观察到的混合抗菌化合物的协同效应相反，这是一种主要不同的机制，其中 TZ 直接作用于膜相关的 AMP，促进其生物活性螺旋构象。模型囊泡研究表明，与无染料 DHVAR4 相比，肽-TZ复合物更容易与双层头基区域的磷酸酯部分形成氢键，从而导致更受控的双层融合机制和协同的严重细胞损伤。AMP 被认为是对抗强大的抗生素耐药性细菌感染的有希望的化合物；然而，我们对它们知之甚少体内行动，特别是关于它们如何与其他化学试剂相互作用。当前的示例说明了食用染料如何调节 AMP 活性，这有望激发针对消化道微生物感染的改进疗法。结果还表明，天然 AMP 的结构和功能可以通过小化合物进行控制，这也可能为未来基于肽的抗菌剂设计提供新的战略概念。