Precise spatial structure impacts antimicrobial susceptibility of S. aureus in polymicrobial wound infections

Area of Science:

• Microbial Ecology
• Wound Infections
• Bacterial Interactions

Background:

• Microbial communities shape ecosystem function through member interactions.
• Chronic wound infections often involve polymicrobial communities, like Staphylococcus aureus and Pseudomonas aeruginosa.
• Previous studies on S. aureus and P. aeruginosa interactions used in vitro models, not reflecting the in vivo infection environment.

Purpose of the Study:

• To investigate the role of macro- and micro-scale spatial structures in S. aureus and P. aeruginosa interactions within chronic murine wounds.
• To identify the mechanisms driving spatial structuring and its impact on disease severity and antimicrobial tolerance.

Main Methods:

• Characterization of S. aureus and P. aeruginosa interactions in chronic murine wound models.
• High-resolution imaging to visualize microbial distribution.
• Quantitative framework to analyze spatial structures at macro (mm) and micro (µm) scales.
• Assessment of antimicrobial production by P. aeruginosa (2-heptyl-4-hydroxyquinoline N-oxide and pyocyanin).
• Evaluation of S. aureus tolerance to aminoglycoside and vancomycin antibiotics in relation to spatial structure.

Main Results:

• S. aureus and P. aeruginosa coexist at high densities in murine wounds, forming a patchy distribution occupying only 5-25% of the wound volume.
• A precise spatial structure at both macro- and micro-scales was identified, primarily mediated by P. aeruginosa's production of 2-heptyl-4-hydroxyquinoline N-oxide.
• Pyocyanin, another P. aeruginosa antimicrobial, did not significantly impact spatial structure.
• The identified spatial structure enhanced S. aureus tolerance to aminoglycoside antibiotics but not vancomycin.

Conclusions:

• Spatial structure is a critical factor in the biogeography of coinfected chronic wounds.
• P. aeruginosa's production of 2-heptyl-4-hydroxyquinoline N-oxide dictates the spatial arrangement of S. aureus and P. aeruginosa.
• Microbial spatial organization in wounds significantly influences bacterial tolerance to specific antibiotics, with implications for treatment strategies.