Trained immunity in recurrent Staphylococcus aureus infection promotes bacterial persistence

Area of Science:

• Microbiology
• Immunology
• Veterinary Medicine

Background:

• Bacterial persister cells are dormant, antibiotic-tolerant subpopulations posing infection control challenges.
• Understanding antibiotic persistence mechanisms is vital for developing effective treatments.

Purpose of the Study:

• To investigate the link between prior infection history and antibiotic tolerance in bovine mastitis.
• To elucidate the role of trained immunity in Staphylococcus aureus persistence.

Main Methods:

• Studied the association between tolerance frequency and infection history in bovine mastitis models.
• Investigated Staphylococcus aureus tolerance to rifampicin in vitro and in vivo following prior infection.
• Analyzed the role of trained immunity and fumarate accumulation in S. aureus persistence.
• Evaluated combination therapy with metformin and rifampicin for recurrent S. aureus infections.

Main Results:

• Previous S. aureus infection significantly increased S. aureus tolerance to rifampicin.
• Trained immunity was identified as a key contributor to rifampicin persistence.
• Fumarate accumulation, induced by trained immunity, mediated S. aureus persistence.
• Combination therapy with metformin and rifampicin effectively eradicated persisters and reduced disease severity.

Conclusions:

• Trained immunity is mechanistically linked to Staphylococcus aureus persistence in recurrent bovine infections.
• Trained immunity represents a viable therapeutic target for combating persistent bacterial pathogens.