What is the mechanism by which Fusobacterium nucleatum depletes glutathione (GSH) in gastric cancer cells?

Label:chem

Topic
The study aims to elucidate the mechanistic link between F. nucleatum infection and GSH depletion in GC cells. GSH is a critical antioxidant that maintains redox homeostasis in cells, and its depletion can lead to oxidative stress and promote tumor progression.

From: "Fusobacterium nucleatum Infection Drives Glutathione Depletion in Gastric Cancer: Integrated Multi-Omics and Experimental Validation", Microorganisms 2025, 13(8), 1907;
Answer
Fusobacterium nucleatum depletes GSH in GC cells through two primary mechanisms: (1) synthesis inhibition by downregulating the expression of glutathione synthetase (GSS), and (2) metabolic consumption due to increased oxidative stress. The infection leads to a decrease in intracellular GSH levels, accompanied by a reduction in GSS mRNA expression and reactive oxygen species (ROS) accumulation. This suggests that F. nucleatum may interfere with GSH synthesis and promote oxidative stress, contributing to GC progression.
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