阿米卡星
美罗培南
铜绿假单胞菌
代谢组学
药理学
代谢途径
氨基糖苷
磷酸戊糖途径
微生物学
抗生素
新陈代谢
生物
生物化学
化学
细菌
糖酵解
抗生素耐药性
生物信息学
遗传学
作者
Hai Yang,Zhen Huang,Jiali Yue,Jianqi Chen,Mingming Yu,Qu Chengming
标识
DOI:10.3389/fcimb.2023.1327452
摘要
The treatment of Pseudomonas aeruginosa infection often involves the combined use of β-lactam and aminoglycoside antibiotics. In this study, we employed metabolomic analysis to investigate the mechanism responsible for the synergistic activities of meropenem/amikacin combination therapy against multidrug-resistant P. aeruginosa strains harboring OXA-50 and PAO genes. Antibiotic concentrations for meropenem (2 mg/L) monotherapy, amikacin (16 mg/L) monotherapy, and meropenem/amikacin (2/16 mg/L) combination therapy were selected based on clinical breakpoint considerations. Metabolomic analysis revealed significant alterations in relevant metabolites involved in bacterial cell membrane and cell wall synthesis within 15 min of combined drug administration. These alterations encompassed various metabolic pathways, including fatty acid metabolism, peptidoglycan synthesis, and lipopolysaccharide metabolism. Furthermore, at 1 h and 4 h, the combination therapy exhibited significant interference with amino acid metabolism, nucleotide metabolism, and central carbon metabolism pathways, including the tricarboxylic acid cycle and pentose phosphate pathway. In contrast, the substances affected by single drug administration at 1 h and 4 h demonstrated a noticeable reduction. Meropenem/amikacin combination resulted in notable perturbations of metabolic pathways essential for survival of P. aeruginosa , whereas monotherapies had comparatively diminished impacts.
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