Identification of a novel gene argJ involved in arginine biosynthesis critical for persister formation in...

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Staphylococcus aureus causes persistent infections like chronic wounds and osteomyelitis.
• Understanding S. aureus persistence mechanisms is critical for effective therapies.
• Current knowledge of S. aureus persistence is limited.

Purpose of the Study:

• To identify novel mechanisms underlying Staphylococcus aureus persistence.
• To investigate the role of arginine biosynthesis in S. aureus persister formation.
• To explore potential therapeutic targets for persistent S. aureus infections.

Main Methods:

• High-throughput screening of a Staphylococcus aureus USA300 transposon mutant library.
• Assessing persister formation under various drug and stress conditions.
• Evaluating bacterial virulence in mouse and C. elegans models.

Main Results:

• A transposon insertion in argJ, an arginine biosynthesis gene, significantly impaired S. aureus persister formation.
• Arginine supplementation and genetic complementation restored persistence in the argJ mutant.
• ArgJ active site mutations abolished persistence, and arg operon genes were upregulated under stress.
• The argJ mutant exhibited reduced virulence in both mouse and C. elegans models.

Conclusions:

• Arginine metabolism, mediated by ArgJ, represents a novel mechanism for Staphylococcus aureus persistence.
• Targeting arginine metabolism could lead to new therapeutic strategies against persistent S. aureus infections.
• This study provides crucial insights into S. aureus persistence and potential drug targets.