Integration of metabolomics and transcriptomics analyses reveals sphingosine-1-phosphate-mediated S1PR2/PI3K/Akt pathway involved in Talaromyces marneffei infection of macrophages

Talaromycosis is a fatal mycosis caused by the thermally dimorphic fungus Talaromyces marneffei (T. marneffei). The pathogenic mechanisms of talaromycosis are still poorly understood. This work combined metabolomics, transcriptomics, and verification experiments in vivo and in vitro to detect metabo...

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Bibliographic Details
Published in:Microbial pathogenesis 2023-02, Vol.175, p.105985-105985, Article 105985
Main Authors: Yang, Lu-Hui, Dong, Rong-Jing, Lu, You-Wang, Wang, Hong-Mei, Kuang, Yi-Qun, Wang, Rui-Rui, Li, Yu-Ye
Format: Article
Language:English
Subjects:
Macrophages - microbiology
Metabolomics
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Proto-Oncogene Proteins c-akt - metabolism
S1P
Sphingolipid
Sphingolipids - metabolism
T. marneffei
Talaromyces - genetics
Transcriptome
Transcriptomics
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Summary:Talaromycosis is a fatal mycosis caused by the thermally dimorphic fungus Talaromyces marneffei (T. marneffei). The pathogenic mechanisms of talaromycosis are still poorly understood. This work combined metabolomics, transcriptomics, and verification experiments in vivo and in vitro to detect metabolic profiles and differentially expressed genes (DEGs) in T. marneffei infected and uninfected macrophages to explore possible pathogenesis and underlying mechanisms. A total of 256 differential metabolites (117 up-regulated and 148 down-regulated) and 1320 DEGs (1286 up-regulated and 34 down-regulated) were identified between the two groups. Integrative metabolomics and transcriptomics analysis showed sphingolipid signaling pathway is the most influential. Verification experiments showed that compared with the control group, the production of sphingosine-1-phosphate (S1P) and the expression of the S1PR1, S1PR2, phosphor-PI3K, and phosphor-Akt genes involved in the sphingolipid signaling pathway have significantly increased in the T. marneffei infection group (p 
ISSN:0882-4010
1096-1208
DOI:10.1016/j.micpath.2023.105985