Activity of the Caged Xanthone Morellic Acid against Vancomycin-Resistant Enterococcus Infection by Targeting the Bacterial Membrane.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-10-10 DOI:10.1021/acs.jnatprod.4c00425

Dong-Mei Tang, Zhao-Jie Wang, Wen-Biao Zu, Yue-Ming Jiang, Yan-Yan Zhu, Mei-Zhen Wei, Xiao-Dong Luo

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Abstract

Vancomycin-resistant Enterococcus (VRE) is an important nosocomial opportunistic pathogen that is associated with multidrug resistance. Here, we demonstrate that morellic acid inhibits VRE by restoring its sensitivity to vancomycin and ampicillin with low drug resistance and efficient biofilm clearance effects. Morellic acid binds to inner membrane phospholipids, such as phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) of VRE, such that the fluidity and proton-motive force (PMF) interfere with the damaged inner membrane, causing intracellular reactive oxygen species (ROS) accumulation and bacterial death. Transcriptional analyses supported this effect on inner membrane-related pathways such as fatty acid biosynthesis and glycerophospholipid metabolism. Moreover, morellic acid significantly eliminated residual bacteria in the spleen, liver, kidneys, and abdominal effusion in mice. Our findings indicate the potential applications of morellic acid as an antibacterial agent or adjuvant for treating VRE infections.

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笼黄酮莫来酸通过靶向细菌膜对抗耐万古霉素肠球菌感染的活性

耐万古霉素肠球菌（VRE）是一种重要的院内机会性病原体，与多种药物耐药性有关。在这里，我们证明了莫来酸对 VRE 的抑制作用，它能恢复 VRE 对万古霉素和氨苄西林的敏感性，并具有低耐药性和高效的生物膜清除效果。莫来酸能与 VRE 的内膜磷脂结合，如磷脂酰乙醇胺（PE）、磷脂酰甘油（PG）和心磷脂（CL），从而干扰受损内膜的流动性和质子动力（PMF），导致细胞内活性氧（ROS）积累和细菌死亡。转录分析支持这种对脂肪酸生物合成和甘油磷脂代谢等内膜相关途径的影响。此外，月桂酸还能明显消除小鼠脾脏、肝脏、肾脏和腹腔积液中的残留细菌。我们的研究结果表明，麦卢卡酸可作为一种抗菌剂或辅助剂用于治疗 VRE 感染。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.