{"title":"表观遗传修饰和代谢基因突变驱动对刺激性抗生素的抗性进化。","authors":"Hui Lin, Donglin Wang, Qiaojuan Wang, Jie Mao, Lutong Yang, Yaohui Bai, Jiuhui Qu","doi":"10.1038/s44320-025-00087-4","DOIUrl":null,"url":null,"abstract":"<p><p>The antibiotic resistance crisis, fueled by misuse and bacterial evolution, is a major global health threat. Traditional perspectives tie resistance to drug target mechanisms, viewing antibiotics as mere growth inhibitors. New insights revealed that low-dose antibiotics may also serve as signals, unexpectedly promoting bacterial growth. Yet, the development of resistance under these conditions remains unknown. Our study investigated resistance evolution under stimulatory antibiotics and uncovered new genetic mechanisms of resistance linked to metabolic remodeling. We documented a shift from a fast, reversible mechanism driven by methylation in central metabolic pathways to a slower, stable mechanism involving mutations in key metabolic genes. Both mechanisms contribute to a metabolic profile transition from glycolysis to rapid gluconeogenesis. In addition, our findings demonstrated that rising environmental temperatures associated with metabolic evolution accelerated this process, increasing the prevalence of metabolic gene mutations, albeit with a trade-off in interspecific fitness. These findings expand beyond the conventional understanding of resistance mechanisms, proposing a broader metabolic mechanism within the selective window of stimulatory sub-MIC antibiotics, particularly in the context of climate change.</p>","PeriodicalId":18906,"journal":{"name":"Molecular Systems Biology","volume":" ","pages":""},"PeriodicalIF":8.5000,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Epigenetic modifications and metabolic gene mutations drive resistance evolution in response to stimulatory antibiotics.\",\"authors\":\"Hui Lin, Donglin Wang, Qiaojuan Wang, Jie Mao, Lutong Yang, Yaohui Bai, Jiuhui Qu\",\"doi\":\"10.1038/s44320-025-00087-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The antibiotic resistance crisis, fueled by misuse and bacterial evolution, is a major global health threat. Traditional perspectives tie resistance to drug target mechanisms, viewing antibiotics as mere growth inhibitors. New insights revealed that low-dose antibiotics may also serve as signals, unexpectedly promoting bacterial growth. Yet, the development of resistance under these conditions remains unknown. Our study investigated resistance evolution under stimulatory antibiotics and uncovered new genetic mechanisms of resistance linked to metabolic remodeling. We documented a shift from a fast, reversible mechanism driven by methylation in central metabolic pathways to a slower, stable mechanism involving mutations in key metabolic genes. Both mechanisms contribute to a metabolic profile transition from glycolysis to rapid gluconeogenesis. In addition, our findings demonstrated that rising environmental temperatures associated with metabolic evolution accelerated this process, increasing the prevalence of metabolic gene mutations, albeit with a trade-off in interspecific fitness. These findings expand beyond the conventional understanding of resistance mechanisms, proposing a broader metabolic mechanism within the selective window of stimulatory sub-MIC antibiotics, particularly in the context of climate change.</p>\",\"PeriodicalId\":18906,\"journal\":{\"name\":\"Molecular Systems Biology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":8.5000,\"publicationDate\":\"2025-01-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Systems Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1038/s44320-025-00087-4\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Systems Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s44320-025-00087-4","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Epigenetic modifications and metabolic gene mutations drive resistance evolution in response to stimulatory antibiotics.
The antibiotic resistance crisis, fueled by misuse and bacterial evolution, is a major global health threat. Traditional perspectives tie resistance to drug target mechanisms, viewing antibiotics as mere growth inhibitors. New insights revealed that low-dose antibiotics may also serve as signals, unexpectedly promoting bacterial growth. Yet, the development of resistance under these conditions remains unknown. Our study investigated resistance evolution under stimulatory antibiotics and uncovered new genetic mechanisms of resistance linked to metabolic remodeling. We documented a shift from a fast, reversible mechanism driven by methylation in central metabolic pathways to a slower, stable mechanism involving mutations in key metabolic genes. Both mechanisms contribute to a metabolic profile transition from glycolysis to rapid gluconeogenesis. In addition, our findings demonstrated that rising environmental temperatures associated with metabolic evolution accelerated this process, increasing the prevalence of metabolic gene mutations, albeit with a trade-off in interspecific fitness. These findings expand beyond the conventional understanding of resistance mechanisms, proposing a broader metabolic mechanism within the selective window of stimulatory sub-MIC antibiotics, particularly in the context of climate change.
期刊介绍:
Systems biology is a field that aims to understand complex biological systems by studying their components and how they interact. It is an integrative discipline that seeks to explain the properties and behavior of these systems.
Molecular Systems Biology is a scholarly journal that publishes top-notch research in the areas of systems biology, synthetic biology, and systems medicine. It is an open access journal, meaning that its content is freely available to readers, and it is peer-reviewed to ensure the quality of the published work.