A defect in menadione biosynthesis induces global changes in gene expression in Staphylococcus aureus

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Staphylococcus aureus relies on electron transport phosphorylation for energy under aerobic conditions.
• The menD gene is crucial for the menaquinone biosynthesis pathway, essential for electron transport.

Purpose of the Study:

• To investigate the global gene expression changes in Staphylococcus aureus caused by a menD mutation.
• To understand the metabolic adaptations of the menD mutant, particularly its energy generation strategies.

Main Methods:

• High-resolution two-dimensional protein gel electrophoresis.
• Full-genome DNA microarrays.
• Comparative analysis of gene expression patterns between wild-type, menD, and hemB mutants.

Main Results:

• The menD mutation induced an anaerobic gene expression profile, upregulating glycolysis and fermentation pathways while downregulating the tricarboxylic acid (TCA) cycle.
• Genes involved in nitrate respiration and the arginine deiminase pathway were significantly increased in the menD mutant.
• Distinct differences in the expression of specific anaerobic enzymes were observed between menD and hemB mutants.

Conclusions:

• The menD mutant generates ATP primarily through substrate phosphorylation, similar to the hemB mutant, indicating a defect in electron transport phosphorylation.
• The menD mutant exhibits altered carbon source utilization, with impaired ability to use TCA cycle intermediates.
• Oxygen depletion and menD/hemB mutations differentially regulate specific anaerobic pathways, including nitrate respiration.