Xiamen Key Laboratory of Indoor Air and Health, Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Road, Xiamen 361021, China.
Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, MOE Key Laboratory of Tumor Molecular Biology, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
Molecules. 2024 May 25;29(11):2504. doi: 10.3390/molecules29112504.
Metabolic reprogramming mediates antibiotic efficacy. However, metabolic adaptation of microbes evolving from antibiotic sensitivity to resistance remains undefined. Therefore, untargeted metabolomics was conducted to unveil relevant metabolic reprogramming and potential intervention targets involved in gentamicin resistance. In total, 61 metabolites and 52 metabolic pathways were significantly altered in gentamicin-resistant . Notably, the metabolic reprogramming was characterized by decreases in most metabolites involved in carbohydrate and amino acid metabolism, and accumulation of building blocks for nucleotide synthesis in gentamicin-resistant . Meanwhile, fatty acid metabolism and glycerolipid metabolism were also significantly altered in gentamicin-resistant . Additionally, glycerol, glycerol-3-phosphate, palmitoleate, and oleate were separately defined as the potential biomarkers for identifying gentamicin resistance in . Moreover, palmitoleate and oleate could attenuate or even abolished killing effects of gentamicin on , and separately increased the minimum inhibitory concentration of gentamicin against by 2 and 4 times. Furthermore, palmitoleate and oleate separately decreased intracellular gentamicin contents, and abolished gentamicin-induced accumulation of reactive oxygen species, indicating involvement of gentamicin metabolism and redox homeostasis in palmitoleate/oleate-promoted gentamicin resistance in . This study identifies the metabolic reprogramming, potential biomarkers and intervention targets related to gentamicin resistance in bacteria.
代谢重编程介导抗生素疗效。然而，从抗生素敏感性进化到耐药性的微生物的代谢适应仍然不明确。因此，进行了非靶向代谢组学研究，以揭示与庆大霉素耐药相关的相关代谢重编程和潜在的干预靶点。在庆大霉素耐药中，总共鉴定出 61 种代谢物和 52 种代谢途径发生了显著变化。值得注意的是，代谢重编程的特征是参与碳水化合物和氨基酸代谢的大多数代谢物减少，核苷酸合成的构建块在庆大霉素耐药中积累。同时，庆大霉素耐药中脂肪酸代谢和甘油磷脂代谢也发生了显著改变。此外，甘油、甘油-3-磷酸、棕榈油酸和油酸分别被定义为鉴定庆大霉素耐药的潜在生物标志物。此外，棕榈油酸和油酸可减弱甚至消除庆大霉素对的杀伤作用，分别使庆大霉素对的最小抑菌浓度增加 2 倍和 4 倍。此外，棕榈油酸和油酸分别降低了细胞内庆大霉素含量，并消除了庆大霉素诱导的活性氧积累，表明庆大霉素代谢和氧化还原平衡参与了棕榈油酸/油酸促进庆大霉素耐药。本研究确定了与细菌中庆大霉素耐药相关的代谢重编程、潜在生物标志物和干预靶点。
