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Pneumococcal H₂O₂ Reshapes Mitochondrial Function and Reprograms Host Cell Metabolism

GSE301606 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2025/09/30 Platform GPL11154
Summary
Streptococcus pneumoniae (Spn), a primary cause of pneumonia, induces acute lung parenchymal damage through a unique metabolic pathway generating hydrogen peroxide (H2O2) as a byproduct. This study demonstrates that Spn-derived H2O2, primarily produced by pyruvate oxidase (SpxB), inhibits key tricarboxylic acid (TCA) cycle enzymes (aconitase, glutamate dehydrogenase, and α-ketoglutarate dehydrogenase) in lung epithelial cells, leading to citrate accumulation and diminished NADH production for oxidative phosphorylation. RNA sequencing reveals SpxBdependent upregulation of glycolytic genes (HIF1A, IER3, HK2, PFKP), restricting pyruvate entry into the TCA cycle and increasing glucose consumption and lactate/acetate production, indicative of a Warburg-like metabolic shift that enhances bacterial survival. Notably, mitochondrial membrane potential remains largely preserved, with minimal apoptosis despite Spn-induced stress. These findings uncover a novel mechanism of Spn-driven host metabolic reprogramming, highlighting potential therapeutic targets for pneumococcal diseases.
Published in
Pneumococcal H₂O₂ reshapes mitochondrial function and reprograms host cell metabolism
Scasny A, Alibayov B, Hoang N et al. · mBio 2025 · PMID 41171083 · doi:10.1128/mbio.02019-25
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Also filed as BioProject PRJNA1285711 and SRA study SRP598220. Searching any of these in the dataset finder brings you back here.

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