Human serum triggers antibiotic tolerance in Staphylococcus aureus

Area of Science:

• Microbiology
• Infectious Diseases
• Pharmacology

Background:

• Staphylococcus aureus infections are difficult to treat, often leading to persistent or relapsing infections.
• Understanding how the host environment affects antibiotic treatment is crucial for improving outcomes.

Purpose of the Study:

• To investigate the impact of human serum on Staphylococcus aureus antibiotic susceptibility.
• To elucidate the mechanisms behind serum-induced antibiotic tolerance.

Main Methods:

• Incubation of S. aureus in human serum and laboratory media.
• Assessment of antibiotic susceptibility, particularly to daptomycin.
• Investigation of molecular mechanisms including host defense peptides (LL-37), the GraRS two-component system, and cardiolipin abundance.

Main Results:

• Human serum induces significant tolerance in S. aureus to daptomycin and other antibiotics.
• Serum-induced daptomycin tolerance is mediated by two independent pathways: LL-37/GraRS-dependent peptidoglycan accumulation and GraRS-independent cardiolipin increase.
• Blocking both mechanisms restores daptomycin susceptibility in S. aureus cultured in serum.

Conclusions:

• Host factors in serum profoundly modulate bacterial antibiotic susceptibility.
• Specific mechanisms, including host defense peptides and membrane lipid composition, contribute to antibiotic tolerance.
• Targeting these host-mediated tolerance mechanisms could be a strategy for combination therapy against S. aureus infections.