Metabolomic analysis reveals an important role of sphingosine 1-phosphate in the development of HFMD due to EV-A71 infection.

IF 4.1 2区 医学 Q2 MICROBIOLOGY
Wangquan Ji, Dejian Dang, Guangyuan Zhou, Ling Tao, Tiantian Sun, Dong Li, Cheng Cheng, Huifen Feng, Jinzhao Long, Shuaiyin Chen, Haiyan Yang, Guangcai Duan, Yuefei Jin
{"title":"Metabolomic analysis reveals an important role of sphingosine 1-phosphate in the development of HFMD due to EV-A71 infection.","authors":"Wangquan Ji, Dejian Dang, Guangyuan Zhou, Ling Tao, Tiantian Sun, Dong Li, Cheng Cheng, Huifen Feng, Jinzhao Long, Shuaiyin Chen, Haiyan Yang, Guangcai Duan, Yuefei Jin","doi":"10.1128/aac.01272-24","DOIUrl":null,"url":null,"abstract":"<p><p>Hand, foot, and mouth disease (HFMD) is a serious pediatric infectious disease that causes immeasurable physical and mental health burdens. Currently, there is a lack of information on the mechanisms of HFMD severity and early diagnosis. We performed metabolomic profiling of sera from 84 Enterovirus A71 (EV-A71) infections and 45 control individuals. Targeted metabolomics assays were employed to further validate some of the differential metabolic molecules. We identified significant molecular changes in the sera of HFMD patients compared to healthy controls (HCs). A total of 54, 60, 35, and 62 differential metabolites were screened between mild cases and HCs, severe cases and HCs, severe cases and mild cases, and among the three groups, respectively. These differential metabolites implicated dysregulation of the tricarboxylic acid cycle, alanine, aspartate, and glutamate metabolism, and valine, leucine, and isoleucine biosynthesis. The diagnostic panel based on some overlapped differential metabolites could effectively discriminate severe cases from mild cases with an AUC of 0.912 (95% CI: 0.85-0.97) using the logistic regression model. Next, we found the elevation of serum sphingosine 1-phosphate (S1P) level in EV-A71 infection mice, which was similar to clinical observation. Importantly, after blocking the release of S1P by MK571, the clinical symptoms and survival of mice were significantly improved, involving the reduction of leukocyte infiltration in infected brain tissues. Collectively, our data provided a landscape view of metabolic alterations in EV-A71 infected children and revealed regulating S1P metabolism was an exploitable therapeutic target against EV-A71 infection.</p>","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0127224"},"PeriodicalIF":4.1000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antimicrobial Agents and Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1128/aac.01272-24","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Hand, foot, and mouth disease (HFMD) is a serious pediatric infectious disease that causes immeasurable physical and mental health burdens. Currently, there is a lack of information on the mechanisms of HFMD severity and early diagnosis. We performed metabolomic profiling of sera from 84 Enterovirus A71 (EV-A71) infections and 45 control individuals. Targeted metabolomics assays were employed to further validate some of the differential metabolic molecules. We identified significant molecular changes in the sera of HFMD patients compared to healthy controls (HCs). A total of 54, 60, 35, and 62 differential metabolites were screened between mild cases and HCs, severe cases and HCs, severe cases and mild cases, and among the three groups, respectively. These differential metabolites implicated dysregulation of the tricarboxylic acid cycle, alanine, aspartate, and glutamate metabolism, and valine, leucine, and isoleucine biosynthesis. The diagnostic panel based on some overlapped differential metabolites could effectively discriminate severe cases from mild cases with an AUC of 0.912 (95% CI: 0.85-0.97) using the logistic regression model. Next, we found the elevation of serum sphingosine 1-phosphate (S1P) level in EV-A71 infection mice, which was similar to clinical observation. Importantly, after blocking the release of S1P by MK571, the clinical symptoms and survival of mice were significantly improved, involving the reduction of leukocyte infiltration in infected brain tissues. Collectively, our data provided a landscape view of metabolic alterations in EV-A71 infected children and revealed regulating S1P metabolism was an exploitable therapeutic target against EV-A71 infection.

求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
10.00
自引率
8.20%
发文量
762
审稿时长
3 months
期刊介绍: Antimicrobial Agents and Chemotherapy (AAC) features interdisciplinary studies that build our understanding of the underlying mechanisms and therapeutic applications of antimicrobial and antiparasitic agents and chemotherapy.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信