Mycoplasma genitalium membrane lipoprotein induces GAPDH malonylation in urethral epithelial cells to regulate cytokine response.

Autor: Wang X; Department of Dermatology, The First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, China., Hu Y; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, China., Li X; Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, China., Huang L; Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, China., Yang Y; Department of Clinical Laboratory, Shanghai Putuo People's Hospital, Tongji University, Shanghai, China., Liu C; Institute of Pathogenic Biology, Hengyang Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, China., Deng Q; Department of Dermatology, The First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, China., Yang P; Department of Dermatology, The First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, China., Li Y; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, China., Zhou Y; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, China., Xiao L; Department of Clinical Laboratory, The Second Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, China., Wu H; Department of Clinical Laboratory, The Second Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, China., He L; Department of Obstetrics and Gynecology, The First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang, China. Electronic address: helu@usc.edu.cn.
Jazyk: angličtina
Zdroj: Microbial pathogenesis [Microb Pathog] 2024 Oct; Vol. 195, pp. 106872. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1016/j.micpath.2024.106872
Abstrakt: Membrane lipoproteins serve as primary pro-inflammatory virulence factors in Mycoplasma genitalium. Membrane lipoproteins primarily induce inflammatory responses by activating Toll-like Receptor 2 (TLR2); however, the role of the metabolic status of urethral epithelial cells in inflammatory response remains unclear. In this study, we found that treatment of uroepithelial cell lines with M. genitalium membrane lipoprotein induced metabolic reprogramming, characterized by increased aerobic glycolysis, decreased oxidative phosphorylation, and increased production of the metabolic intermediates acetyl-CoA and malonyl-CoA. The metabolic shift induced by membrane lipoproteins is reversible upon blocking MyD88 and TRAM. Malonyl-CoA induces malonylation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and malonylated GAPDH could dissociate from the 3' untranslated region of TNF-α and IFN-γ mRNA. This dissociation greatly reduces the inhibitory effect on the translation of TNF-α and IFN-γ mRNA, thus achieving fine-tuning control over cytokine secretion. These findings suggest that GAPDH malonylation following M. genitalium infection is an important inflammatory signal that plays a crucial role in urogenital inflammatory diseases.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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