Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria

Area of Science:

• Microbiology
• Genomics
• Proteomics
• Metabolomics
• Infectious Diseases

Background:

• Severe sepsis and septic shock carry high mortality rates (20-40%) even with optimal care.
• Antibiotic resistance exacerbates sepsis mortality, necessitating novel therapeutic strategies.
• Identifying common bacterial targets is essential for developing effective interventions.

Purpose of the Study:

• To create a comprehensive reference dataset for identifying common bacterial targets in sepsis.
• To investigate the molecular responses of key sepsis pathogens to human serum.

Main Methods:

• Applied a standardized multi-omics framework (genomic, transcriptomic, proteomic, metabolomic) to clinical isolates.
• Studied four major sepsis pathogens: Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pyogenes.
• Exposed bacterial isolates to human serum to analyze molecular signatures.

Main Results:

• A sepsis molecular signature was identified, characterized by increased fatty acid and lipid biosynthesis and metabolism.
• Observed bacterial cell envelope remodeling and nutrient adaptation for osmoprotection.
• Detected cholesterol acquisition across all studied bacterial species.

Conclusions:

• The study provides a detailed, open-access multi-omics dataset for sepsis research.
• Findings highlight conserved bacterial adaptations to serum exposure, offering potential therapeutic targets.
• This resource supports the development of novel diagnostic and therapeutic strategies against sepsis-causing pathogens.