Pneumococcal H₂O₂ reshapes mitochondrial function and reprograms host cell metabolism

Area of Science:

• Microbiology
• Cellular Metabolism
• Pathogenesis

Background:

• *Streptococcus pneumoniae* (Spn) is a major cause of pneumonia.
• Spn pathogenesis involves host metabolic manipulation.
• Mechanisms of Spn-induced metabolic changes are not fully understood.

Purpose of the Study:

• To elucidate the role of Spn-derived hydrogen peroxide (H₂O₂) in host cell metabolism.
• To identify Spn-driven metabolic reprogramming in lung epithelial cells.
• To explore potential therapeutic targets for pneumococcal diseases.

Main Methods:

• *In vitro* studies using lung epithelial cells exposed to Spn.
• Measurement of TCA cycle enzyme activity.
• RNA sequencing to analyze gene expression changes.
• Analysis of mitochondrial function and apoptosis.

Main Results:

• Spn-derived H₂O₂, produced by pyruvate oxidase (SpxB), inhibits key TCA cycle enzymes.
• Spn induces a Warburg-like metabolic shift, upregulating glycolysis and increasing lactate/acetate production.
• Host cell mitochondrial membrane potential is preserved, with minimal apoptosis observed.
• Citrate accumulation and reduced NADH production were noted.

Conclusions:

• Spn actively reprograms host cell metabolism via H₂O₂ to enhance its survival.
• The Warburg-like shift favors bacterial persistence while maintaining host cell integrity.
• Targeting Spn's metabolic pathway offers potential therapeutic strategies for pneumonia.