Chen Yue-Tao, Ma Yan-Mei, Peng Xuan-Xian, Li Hui
State Key Laboratory of Bio-Control, School of Life Sciences, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Guangdong Key Laboratory of Pharmaceutical Functional Genes, Sun Yat-sen University, Guangzhou, China.
Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
Front Microbiol. 2022 Dec 2;13:1071278. doi: 10.3389/fmicb.2022.1071278. eCollection 2022.
Gentamicin is a conventional antibiotic in clinic. However, with the wide use of antibiotics, gentamicin-resistant (E. coli) is an ever-increasing problem that causes infection in both humans and animals. Thus, it is especially important to restore gentamicin-mediated killing efficacy.
K12 BW25113 cells were passaged in medium with and without gentamicin and obtain gentamicin-resistant (K12-R ) and control (K12-S) strains, respectively. Then, the metabonomics of the two strains were analyzed by GC-MS approach.
K12-R metabolome was characterized as more decreased metabolites than increased metabolites. Meantime, in the most enriched metabolic pathways, almost all of the metabolites were depressed. Alanine, aspartate and glutamate metabolism and glutamine within the metabolic pathway were identified as the most key metabolic pathways and the most crucial biomarkers, respectively. Exogenous glutamine potentiated gentamicin-mediated killing efficacy in glutamine and gentamicin dose-and time-dependent manners in K12-R . Further experiments showed that glutamine-enabled killing by gentamicin was effective to clinically isolated multidrug-resistant .
These results suggest that glutamine provides an ideal metabolic environment to restore gentamicin-mediated killing, which not only indicates that glutamine is a broad-spectrum antibiotic synergist, but also expands the range of metabolites that contribute to the bactericidal efficiency of aminoglycosides.
庆大霉素是临床上常用的抗生素。然而，随着抗生素的广泛使用，耐庆大霉素（大肠杆菌）问题日益严重，导致人类和动物感染。因此，恢复庆大霉素介导的杀菌效果尤为重要。
将K12 BW25113细胞分别在含和不含庆大霉素的培养基中传代，分别获得耐庆大霉素（K12-R）和对照（K12-S）菌株。然后，采用气相色谱-质谱联用（GC-MS）方法分析这两种菌株的代谢组学。
K12-R代谢组的特征是代谢物减少多于增加。同时，在最丰富的代谢途径中，几乎所有代谢物都减少。丙氨酸、天冬氨酸和谷氨酸代谢以及该代谢途径中的谷氨酰胺分别被确定为最关键的代谢途径和最关键的生物标志物。外源性谷氨酰胺在K12-R中以谷氨酰胺和庆大霉素剂量及时间依赖性方式增强庆大霉素介导的杀菌效果。进一步实验表明，谷氨酰胺增强庆大霉素的杀菌作用对临床分离的多重耐药菌有效。
这些结果表明，谷氨酰胺为恢复庆大霉素介导的杀菌作用提供了理想的代谢环境，这不仅表明谷氨酰胺是一种广谱抗生素增效剂，而且扩大了有助于氨基糖苷类杀菌效率的代谢物范围。
