Serum N-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens

Area of Science:

• Biochemistry
• Clinical Diagnostics
• Proteomics

Background:

• Bacteremia, the presence of pathogens in the bloodstream, is a critical precursor to sepsis and is associated with significant morbidity.
• Current diagnostic methods for bacteremia lack the necessary precision, speed, and sensitivity for effective patient stratification.
• Timely detection and stratification of bacteremic patients are crucial for reducing mortality.

Purpose of the Study:

• To investigate the potential of quantitative serum N-glycomics as a diagnostic tool for stratifying patients with bacteremia.
• To differentiate patients infected with specific bacterial pathogens (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus viridans) from healthy individuals.

Main Methods:

• Quantitative serum N-glycomics analysis using porous graphitized carbon liquid chromatography tandem mass spectrometry.
• Profiling of 62 N-glycan isomers and 41 glycan compositions using label-free quantitation.
• Application of unsupervised hierarchical clustering and principal component analysis for data interpretation.

Main Results:

• Serum N-glycome data successfully separated bacteremic patients into distinct groups.
• Patients with Pseudomonas aeruginosa infection showed elevated fucosylation, bisecting N-acetylglucosamine (GlcNAc), and reduced sialylation.
• Receiver operating characteristic analyses confirmed that individual N-glycan isomers could effectively stratify bacteremic patients from healthy donors with high accuracy (AUC 0.93-1.00).

Conclusions:

• Serum N-glycome profiling offers a promising new avenue for the diagnosis and stratification of bloodstream infections.
• Specific N-glycan structures serve as potential biomarkers for identifying bacteremia and differentiating causative pathogens.
• This approach has the potential to significantly improve the management and outcomes of patients with bacteremia.