Reduced glutathione levels in Enterococcus faecalis trigger metabolic and transcriptional compensatory adjustments during iron exposure.

This study investigates the bacterium's response to elevated iron levels in the context of glutathione deficiency, a critical low molecular weight antioxidant synthesized within cells. We examined the transcriptomic and metabolic responses of a glutathione synthetase mutant strain (Δgsh) under conditions of increased iron, integrating these data into a genome-scale metabolic model (GSMM).

Our findings reveal that, under glutathione deficiency, E. faecalis markedly reduces intracellular iron levels compared to the wild-type strain, with a reconfiguration of its global transcriptional response to prioritize the expression of genes involved in energy production. This transcriptional shift is associated with alterations in basal metabolites, notably an increase in arginine levels. The GSMM analysis underscores the significance of arginine metabolism as a potential compensatory mechanism for the diminished glutathione content during iron exposure, particularly highlighting the role of the arc operon (anaerobic arginine catabolism) in energy generation.