Dynamic Profiling of Lipoteichoic Acid (LTA) and/or Lipopolysaccharide (LPS) Positive Extracellular Vesicles in Plasma as Diagnostic and Prognostic Biomarkers for Bacterial Infection

Bacterial extracellular vesicles (EVs) are emerging as promising biomarkers for diagnosing bacterial infections. This study explores the diagnostic potential of plasma EVs carrying bacterial lipopolysaccharide (LPS) or lipoteichoic acid (LTA). Using immunoelectron microscopy (IEM) and nanoflow cytometry (nano-FCM), LTA is confirmed on cytoplasmic membrane vesicles (CMVs) from Gram-positive bacteria and LPS on outer membrane vesicles (OMVs) from Gram-negative bacteria, and quantified LTA-positive or LPS-positive (LTA⁺/LPS⁺) EVs in plasma. Bacterial infection models showed higher levels of LTA⁺/LPS⁺ EVs in infected groups compared to controls, correlating with increased inflammatory markers like interlinleukin-6 ( IL-6) and c-reactive protein (CRP). Clinical samples from patients with bloodstream infections also revealed elevated LTA⁺/LPS⁺ EV levels. These EVs can distinguish bacterial infections from non-bacterial ones, differentiate between Gram-positive and Gram-negative infections, and reflect disease progression and treatment response. The findings suggest that LPS⁺/LTA⁺ EVs hold strong potential as novel diagnostic and prognostic biomarkers, offering a new approach for early detection and management of bacterial infections.