Pathoadapative Genomic Determinants of Staphylococcus aureus Community Skin Infections and Nasal Colonization.

Area of Science:

• Microbiology
• Genomics
• Infectious Diseases

Background:

• Staphylococcus aureus is a major cause of skin and soft tissue infections (SSTIs).
• The genomic basis for S. aureus transitioning from nasal colonization to invasive disease is not fully understood.
• Understanding these adaptations is crucial for developing new treatments.

Purpose of the Study:

• To identify specific genomic adaptations in S. aureus associated with SSTIs.
• To correlate bacterial genetic features with infection severity.
• To explore the role of nasal microbiota in S. aureus pathoadaptation.

Main Methods:

• Genome sequencing and analysis of 157 S. aureus isolates (SSTI and nasal).
• Genome-wide association studies (GWAS) and non-synonymous single-nucleotide variant (NSNV) profiling.
• Machine learning for identifying infection classifiers and a novel Purulent Ulcer Skin (PUS) score for severity quantification.

Main Results:

• SSTI isolates showed enrichment in genes for nitrogen assimilation, purine biosynthesis, menaquinone production, and anaerobic respiration.
• Phage-linked metabolic genes and alpha/beta-hydrolase encoding genes were associated with increased infection severity and larger wound size.
• Machine learning identified metabolic loci like purL as key infection classifiers, with NSNVs in stress resistance and cytolytic genes.

Conclusions:

• Genomic adaptations in metabolic and regulatory pathways facilitate S. aureus transition to invasive SSTIs.
• Specific genes and genomic features correlate with infection severity, offering potential therapeutic targets.
• Nasal commensals possess adaptive capacity for pathogenic transition, highlighting the importance of the nasal microbiome in infection dynamics.