Key points
- Heme, an iron-containing molecule, plays a previously unknown role in bacterial H2S signaling.
- Heme binding to transcription factors catalyzes the conversion of H2S to polysulfide, thereby modifying the protein.
- This modification alters gene expression, impacting stress tolerance and antibiotic resistance.
- The process is oxygen-dependent; heme blocks the reaction in oxygen-deficient conditions.
Japanese researchers have uncovered a critical role for heme in bacterial resistance to antibiotics, revealing a novel mechanism of hydrogen sulfide (H2S) signaling. Their study, published in Redox Biology, focuses on how heme, traditionally known for its role in oxygen transport, acts as a catalyst in a process that directly impacts bacterial gene expression and survival.
The team, led by Professor Shinji Masuda of the Institute of Science, Tokyo, investigated the transcription factors SqrR and YgaV in Rhodobacter capsulatus and Escherichia coli, respectively.
Their research demonstrates that when H2S enters a bacterial cell, heme bound to these transcription factors facilitates a reaction converting H2S into polysulfide. This highly reactive molecule then modifies the transcription factor by forming a tetra-sulfide bridge between cysteine residues. This modification significantly impacts the transcription factor’s ability to bind to DNA, altering gene expression.
Specifically, it leads to increased expression of genes involved in sulfide metabolism, anaerobic respiration, and oxidative stress tolerance, all of which contribute to the development of antibiotic resistance.
Crucially, the researchers found this process is oxygen-dependent. In the absence of oxygen, heme binding prevents the oxidation reaction, effectively suppressing H2S signaling. This oxygen sensitivity provides a potential target for future therapeutic interventions.
The findings offer a new understanding of bacterial responses to environmental stressors and highlight the multifaceted roles of heme within bacterial cells.
The discovery of this previously unknown heme-dependent H2S signaling pathway offers exciting possibilities for the development of novel antibiotics. By targeting this specific mechanism, researchers hope to create new strategies to combat the growing threat of antibiotic resistance.
Future research will investigate the prevalence of this mechanism in other bacterial species and explore the potential involvement of additional signaling molecules.
This work represents a significant advancement in our understanding of bacterial survival mechanisms. It could revolutionize the fight against drug-resistant infections.
