L-Proline protects mice challenged by Klebsiella pneumoniae bacteremia
L-Proline protects mice challenged by Klebsiella pneumoniae bacteremia
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DOI：
10.1016/j.jmii.2019.05.013
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发表时间：
2021-04-22
影响因子：
7.4
通讯作者：
Zhou, Shaosong
中科院分区：
文献类型：
--
作者：
Chen, Xuedong;Qin, Sihua;Zhou, Shaosong
目的：K.肺炎是临床上常见的引起菌血症的病原体，对大多数已知的抗生素无反应，从而累积地加剧经验性治疗失败。对控制肺炎克雷伯菌菌血症的有效策略的需求很高。方法：采用GC/MS代谢组学技术，研究了克雷伯氏菌感染后小鼠体内代谢的变化。结果：与肺炎克雷伯菌（ATCC 43816）感染的小鼠相比，在肺炎菌血症中，从感染中存活的小鼠显示出不同的代谢组学特征。代谢物组差异分析表明，乙二酸、D-葡萄糖、L-谷氨酰胺、肌醇和L-脯氨酸更可能与宿主在K.肺炎菌血症。进一步的途径富集分析表明精氨酸和脯氨酸代谢参与了K.肺炎菌血症。结论：本研究提供了一种从存活宿主体内鉴定代谢标志物的可行策略，并强调了利用代谢标志物治疗肺炎克雷伯菌的可能性。肺炎菌血症。Copyright（C）2019，Taiwan Society of Microbiology.出版社：Elsevier Taiwan LLC
Objective: K. pneumoniae, a common pathogen that frequently causes bacteremia in clinic, is unresponsive to most of known antibiotics, thus cumulatively exacerbating empirical therapy failures. Effective strategies to control Klebsiella pneumoniae bacteremia are in high demand. One possibility is to mobilize host defense mechanisms against bacterial pathogens.Methods: We employed GC/MS-based metabolomics to identify the changes of metabolism in mice challenged by K. pneumoniae (ATCC 43816) bacteremia.Results: Compared with the mice that compromised from K. pneumoniae bacteremia, mice that survived from infection displayed the varied metabolomic profile. The differential analysis of metabolome showed that Ethanedioic acid, D-Glucose, L-Glutamine, Myo-inositol, and L-Proline were more likely associated with the host surviving a K. pneumoniae bacteremia. Further pathway enrichment analysis proposed that arginine and proline metabolism involved in outcome of K. pneumoniae bacteremia. The follow-up data showed that exogenous L-Proline but not D-Proline could decline the loads of Klebsiella pneumonia in infected blood and tissues (lung, liver and spleen) and increase the mouse survival.Conclusion: Our study provides an exercisable strategy of identifying metabolic biomarkers from surviving host and highlights the possibility of utilizing the metabolic biomarker as a therapy for K. pneumoniae bacteremia. Copyright (C) 2019, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC.