The msaABCR Operon Regulates Persister Formation by Modulating Energy Metabolism in Staphylococcus aureus

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• Staphylococcus aureus causes persistent infections due to antibiotic-tolerant persister cells.
• The msaABCR operon is implicated in staphylococcal phenotypes, including persister cell formation.
• Metabolism is crucial for persister cell development.

Purpose of the Study:

• To elucidate the role of the msaABCR operon in regulating energy metabolism and antibiotic tolerance in S. aureus.
• To understand how msaABCR influences metabolic pathways related to persister cell formation.

Main Methods:

• Gene deletion studies of the msaABCR operon.
• Analysis of tricarboxylic acid (TCA) cycle activity.
• Measurement of cellular ATP and NADH content.
• Transcriptomic analysis of target genes (ccpE, ndh2).

Main Results:

• Deletion of msaABCR increased TCA cycle activity, ATP, and NADH content.
• msaABCR (via MsaB) represses ccpE and ndh2 genes, regulating TCA cycle and membrane potential.
• A metabolically hyperactive state was induced upon msaABCR deletion.

Conclusions:

• The msaABCR operon negatively regulates energy metabolism in S. aureus.
• Modulating the msaABCR operon can decrease persister cell formation by inducing metabolic hyperactivity.
• Targeting the msaABCR operon presents a potential strategy to combat persistent S. aureus infections.