Pneumococcal H₂O₂ reshapes mitochondrial function and reprograms host cell metabolism.

ABSTRACT: 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 SpxB-dependent 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 may enha

SUBMITTER: Scasny A 

PROVIDER: S-EPMC12691681 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature