Upregulated Palmitoleate and Oleate Production in Escherichia coli Promotes Gentamicin Resistance

• Published in: Molecules (Basel, Switzerland) Vol. 29; no. 11; p. 2504
• Main Authors: Ye, Guozhu, Fan, Lvyuan, Zheng, Yuhong, Liao, Xu, Huang, Qiansheng, Su, Yubin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.06.2024; MDPI
• Subjects: amino acid metabolism; Amino acids; Anti-Bacterial Agents - pharmacology; antibiotic resistance; Antibiotics; Bacteria; Biomarkers; Carbohydrates; Chromatography; Drug resistance; Drug resistance in microorganisms; Drug Resistance, Bacterial - drug effects; E coli; Escherichia coli - drug effects; Escherichia coli - genetics; Escherichia coli - metabolism; Fatty Acids, Monounsaturated - metabolism; Fatty Acids, Monounsaturated - pharmacology; gentamicin; Gentamicins - metabolism; Gentamicins - pharmacology; Glucose; lipid metabolism; Mass spectrometry; Metabolic Networks and Pathways - drug effects; Metabolism; Metabolites; metabolomics; Metabolomics - methods; Microbial Sensitivity Tests; Neomycin; Oleic Acid - metabolism; Oleic Acid - pharmacology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Scientific imaging; Up-Regulation - drug effects; Water, Underground; China; gentamicin; antibiotic resistance; metabolomics; lipid metabolism; reactive oxygen species; amino acid metabolism
• ISSN: 1420-3049; 1420-3049
• 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 E. coli. 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 E. coli. Meanwhile, fatty acid metabolism and glycerolipid metabolism were also significantly altered in gentamicin-resistant E. coli. Additionally, glycerol, glycerol-3-phosphate, palmitoleate, and oleate were separately defined as the potential biomarkers for identifying gentamicin resistance in E. coli. Moreover, palmitoleate and oleate could attenuate or even abolished killing effects of gentamicin on E. coli, and separately increased the minimum inhibitory concentration of gentamicin against E. coli 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 E. coli. This study identifies the metabolic reprogramming, potential biomarkers and intervention targets related to gentamicin resistance in bacteria.