Integration of metabolomics and transcriptomics analyses reveals sphingosine-1-phosphate-mediated S1PR2/PI3K/Akt pathway involved in Talaromyces marneffei infection of macrophages. (February 2023)

• Record Type: Journal Article
• Authors: Yang, Lu-Hui; Dong, Rong-Jing; Lu, You-Wang; Wang, Hong-Mei; Kuang, Yi-Qun; Wang, Rui-Rui; Li, Yu-Ye
• Is Part Of: Microbial pathogenesis. Volume 175(2023)
• Publication Date: 2023-02
• Subjects: T. marneffei -- Metabolomics -- Transcriptomics -- Sphingolipid -- S1P; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2023.105985
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: 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 < 0.05). T. marneffei activates the S1PR2/PI3K/Akt pathways in J774A.1 macrophage, regulation of the S1P singling might serve as a promising therapeutic strategy for talaromycosis. Highlights: T . marneffei is a thermally dimorphic fungus causes invasive mycosis. T. marneffei caused 256 differential metabolites and 1320 DEGs in macrophages. The sphingolipid signaling pathway is affected in macrophages. S1PR2/PI3K/Akt pathway was activated during the infection of T. marneffei .