禁食诱导的生酮使细菌对抗生素治疗敏感

IF 27.7 1区 生物学 Q1 CELL BIOLOGY
Shujun Cui, Danyang Chong, Yi-Xin Wang, Huixian Tong, Minggui Wang, Guo-Ping Zhao, Liang-Dong Lyu
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引用次数: 0

摘要

空腹代谢是对急性感染的一种常见的动机反应,被认为有利于宿主的生存。本研究表明,禁食可增强由鼠伤寒沙门菌、肺炎克雷伯菌和阴沟肠杆菌引起的小鼠败血症的抗生素治疗,从而增加细菌清除率,改善宿主免疫反应和生存率。这种作用是由禁食诱导的生酮介导的,可以通过抗生素和酮体的联合治疗来替代。我们表明酮体乙酰乙酸酯是一种效应物,通过增加抗生素的致死率和内外膜的通透性,使细菌对抗生素治疗增敏。我们的研究结果表明,乙酰乙酸消耗细菌的氨基酸,特别是带正电的氨基酸和腐胺,导致细胞膜功能障碍和氧化还原相关的死亡。这项研究揭示了生酮在抗生素治疗中的未被认识的作用,以及潜在的基于酮体的细菌性败血症治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Fasting-induced ketogenesis sensitizes bacteria to antibiotic treatment

Fasting-induced ketogenesis sensitizes bacteria to antibiotic treatment
Fasting metabolism is a commonly observed motivational response to acute infections and is conceptualized as being beneficial for host survival. Here, we show that fasting potentiates antibiotic treatment for murine sepsis caused by Salmonella Typhimurium, Klebsiella pneumoniae, and Enterobacter cloacae, resulting in increased bacterial clearance and improved host immune responses and survival. This effect is mediated by fasting-induced ketogenesis and could be alternatively implemented by combination therapy with antibiotics and ketone bodies. We show that the ketone body acetoacetate is an effector that sensitizes bacteria to antibiotic treatment by increasing antibiotic lethality and outer and inner membrane permeability. Our results demonstrate that acetoacetate depletes bacterial amino acids, particularly positively charged amino acids and putrescine, leading to cell membrane malfunctions and redox-related lethality. This study reveals an unrecognized role of ketogenesis in antibiotic treatment and a potential ketone body-based treatment strategy for bacterial sepsis.
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来源期刊
Cell metabolism
Cell metabolism 生物-内分泌学与代谢
CiteScore
48.60
自引率
1.40%
发文量
173
审稿时长
2.5 months
期刊介绍: Cell Metabolism is a top research journal established in 2005 that focuses on publishing original and impactful papers in the field of metabolic research.It covers a wide range of topics including diabetes, obesity, cardiovascular biology, aging and stress responses, circadian biology, and many others. Cell Metabolism aims to contribute to the advancement of metabolic research by providing a platform for the publication and dissemination of high-quality research and thought-provoking articles.
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