Increased intracellular HS levels enhance iron uptake in .

UNLABELLED

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

IMPORTANCE

HS 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 HS 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 HS accumulation and iron uptake activity, a relationship critical for antibiotic resistance. We present additional evidence expanding the role of intracellular HS synthesis in bacterial physiology.