Staphylococcus aureus adapts to exploit collagen-derived proline during chronic infection.

Area of Science:

• Microbiology
• Pulmonary Medicine
• Bacterial Pathogenesis

Background:

• Staphylococcus aureus is a significant cause of lung infections, but current vaccines are ineffective.
• Understanding bacterial adaptation mechanisms is crucial for developing new treatments.

Purpose of the Study:

• To investigate the metabolic adaptations of Staphylococcus aureus during chronic pulmonary infections.
• To identify host-derived factors that support bacterial survival and out-competition.

Main Methods:

• Transcriptomic analysis of clinical S. aureus isolates from initial and chronic infections.
• Metabolomics of bronchoalveolar lavage fluid.
• Fibroblast infection assays and bacterial growth experiments.
• Analysis of bacterial mutant strains.

Main Results:

• Chronic infection isolates showed increased expression of collagenase and proline transporter genes.
• Airway fibroblasts produce collagen during S. aureus infection.
• Degradation of host collagen by bacterial collagenase releases proline, which S. aureus imports for oxidative metabolism.
• Proline metabolism provides a competitive metabolic advantage to host-adapted S. aureus.

Conclusions:

• Staphylococcus aureus adapts to the host environment by utilizing fibroblast-derived collagen for proline, fueling its metabolism.
• This proline metabolic pathway enhances bacterial fitness and out-competition, particularly in fibrotic lung environments.
• Airway repair and fibrosis create a niche favoring S. aureus adaptation and persistent infection.