Increased intracellular H₂S levels enhance iron uptake in Escherichia coli

We investigated the impact of intracellular hydrogen sulfide (H₂S) hyperaccumulation on the transcriptome of Escherichia coli. The wild-type (WT) strain overexpressing mstA, encoding 3-mercaptopyruvate sulfur transferase, produced significantly higher H₂S levels than the control WT strain. The mstA-overexpressing strain exhibited increased resistance to antibiotics, supporting the prior hypothesis that intracellular H₂S contributes to oxidative stress responses and antibiotic resistance. RNA-seq analysis revealed that over 1,000 genes were significantly upregulated or downregulated upon mstA overexpression. The upregulated genes encompassed those associated with iron uptake, including siderophore synthesis and iron import transporters. The mstA-overexpressing strain showed increased levels of intracellular iron content, indicating that H₂S hyperaccumulation affects iron availability within cells. We found that the H₂S-/supersulfide-responsive transcription factor YgaV is required for the upregulated expression of iron uptake genes in the mstA-overexpression conditions. These findings indicate that the expression of iron uptake genes is regulated by intracellular H₂S, which is crucial for oxidative stress responses and antibiotic resistance in E. coli.

Importance: H₂S is recognized as a second messenger in bacteria, playing a vital role in diverse intracellular and extracellular activities, including oxidative stress responses and antibiotic resistance. Both H₂S and iron serve as essential signaling molecules for gut bacteria. However, the intricate intracellular coordination between them, governing bacterial physiology, remains poorly understood. This study unveils a close relationship between intracellular H₂S accumulation and iron uptake activity, a relationship critical for antibiotic resistance. We present additional evidence expanding the role of intracellular H₂S synthesis in bacterial physiology.