Effect of combined oxidative and nitrosative stresses on Staphylococcus aureus transcriptome

Area of Science:

• Microbiology
• Molecular Biology
• Immunology

Background:

• Staphylococcus aureus causes severe infections.
• Innate immunity uses oxidative and nitrosative stresses against pathogens.
• Understanding bacterial stress response is crucial for treatment.

Purpose of the Study:

• Investigate genome-wide transcriptional responses of S. aureus to oxidative stress (hydrogen peroxide), nitrosative stress (GSNO), and their combination.
• Identify key genes and metabolic pathways affected by these stresses.

Main Methods:

• Microarray analysis to assess S. aureus transcriptome.
• Exposure to hydrogen peroxide, S-nitrosoglutathione (GSNO), and combined stresses.
• Analysis of gene expression changes and bacterial viability.

Main Results:

• Oxidative stress (H2O2) primarily affected genes in oxidative detoxification and DNA metabolism.
• Nitrosative stress (GSNO) altered expression of regulatory genes.
• Combined GSNO and H2O2 stresses caused the most significant transcriptomic changes (~10%), affecting cell envelope and iron metabolism genes (e.g., ftnA, dps).
• Combined stress decreased S. aureus viability, which was enhanced by iron and correlated with low siderophore activity.

Conclusions:

• Combined oxidative and nitrosative stresses profoundly impact S. aureus transcription and metabolism.
• These stresses, encountered during phagocytosis, interfere with S. aureus cellular processes.
• Findings provide insights into bacterial defense mechanisms and potential therapeutic targets.