{"title":"Fasting-induced ketogenesis sensitizes bacteria to antibiotic treatment","authors":"Shujun Cui, Danyang Chong, Yi-Xin Wang, Huixian Tong, Minggui Wang, Guo-Ping Zhao, Liang-Dong Lyu","doi":"10.1016/j.cmet.2025.04.006","DOIUrl":null,"url":null,"abstract":"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 <em>Salmonella</em> Typhimurium, <em>Klebsiella pneumoniae</em>, and <em>Enterobacter cloacae</em>, 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.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"24 1","pages":""},"PeriodicalIF":27.7000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell metabolism","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cmet.2025.04.006","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.