Increased survival of Staphylococcus aureus co-cultured with Gram-negative pathogens against antibiotics

Area of Science:

• Microbiology
• Infectious Diseases
• Antimicrobial Resistance

Background:

• Polymicrobial infections often lead to severe disease and worse patient outcomes.
• Understanding interactions between different bacterial species is crucial for effective treatment.

Purpose of the Study:

• To investigate how Gram-negative bacteria co-infection impacts Staphylococcus aureus survival under antibiotic pressure.
• To explore the mechanisms behind enhanced S. aureus survival in polymicrobial settings.

Main Methods:

• In vitro time-kill assays comparing S. aureus monocultures with co-cultures (Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae) treated with ciprofloxacin and vancomycin.
• Analysis of S. aureus survival in bacterial cell pellets versus cell-free supernatant.
• Investigation of Gram-negative bacteria cell density effects and examination of intracellular ATP and rsh expression in surviving S. aureus.

Main Results:

• S. aureus exhibited increased survival against antibiotics when co-cultured with Gram-negative bacteria.
• Enhanced survival was associated with the presence of Gram-negative bacterial cell pellets, not secreted factors.
• Higher Gram-negative bacteria cell density correlated with increased S. aureus survival.
• Co-culture with Acinetobacter baumannii led to reduced intracellular ATP and increased rsh expression in S. aureus.

Conclusions:

• Gram-negative bacteria enhance Staphylococcus aureus survival against antibiotics, a phenomenon not mediated by secreted factors.
• Bacterial cell-to-cell contact or proximity appears critical for this protective effect.
• Increased antibiotic persistence in polymicrobial infections is a significant factor contributing to treatment failure.