Metabolomics Method in Understanding and Sensitizing Carbapenem-Resistant Acinetobacter baumannii to Meropenem
文献类型： 外文期刊
作者： Li, Xia 1 ; Feng, Dingyun 1 ; Zhou, Jianxia 1 ; Wu, Wenbin 1 ; Zheng, Wenzheng 1 ; Gan, Wenlei 1 ; Jiang, Ming 3 ; Li, Hui 2 ; Peng, Xuanxian 2 ; Zhang, Tiantuo 1 ;
作者机构： 1.Sun Yat Sen Univ, Affiliated Hosp 3, Inst Resp Dis, Dept Pulm & Crit Care Med, Guangzhou 510630, Peoples R China
2.Sun Yat Sen Univ, Sch Life Sci, Guangzhou 510275, Peoples R China
3.Guangdong Acad Agr Sci, Inst Anim Sci, Guangzhou 510640, Peoples R China
关键词： carbapenem-resistantA. baumannii; reprogramming metabolomics; Meropenem; ATP; TCA cycle
期刊名称：ACS INFECTIOUS DISEASES （ 影响因子：5.3； 五年影响因子：5.1 ）
ISSN： 2373-8227
年卷期： 2023 年 10 卷 1 期
页码：
收录情况： SCI
摘要： Carbapenem-resistant Acinetobacter baumannii (CRAB) strains are prevalent worldwide and represent a major threat to public health. However, treatment options for infections caused by CRAB are very limited as they are resistant to most of the commonly used antibiotics. Consequently, understanding the mechanisms underlying carbapenem resistance and restoring bacterial susceptibility to carbapenems hold immense importance. The present study used gas chromatography-mass spectrometry (GC-MS)-based metabolomics to investigate the metabolic mechanisms of antibiotic resistance in clinically isolated CRAB. Inactivation of the pyruvate cycle and purine metabolism is the most typical characteristic of CRAB. The CRAB exhibited a reduction in the activity of enzymes involved in the pyruvate cycle, proton motive force, and ATP levels. This decline in central carbon metabolism resulted in a decrease in the metabolic flux of the alpha-ketoglutarate-glutamate-glutamine pathway toward purine metabolism, ultimately leading to a decline in adenine nucleotide interconversion. Exogenous adenosine monophosphate (AMP) and adenosine triphosphate (ATP) enhance the killing efficacy of Meropenem against CRAB. The combination of ATP and Meropenem also has a synergistic effect on eliminating CRAB persisters and the biofilm, as well as protecting mice against peritonitis-sepsis. This study presents a novel therapeutic modality to treat infections caused by CRAB based on the metabolism reprogramming strategy.
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