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Updated: Sep 16, 2025
Author Spotlight: Advancing the Analysis of Plasma Extracellular Vesicle Proteome for Cardiovascular Biomarker Studies
Published on: January 31, 2025
Proteomic Profiling of Acoustically Isolated Extracellular Vesicles from Blood Plasma during Murine Bacterial Sepsis
Axel Broman1, Yashuan Chao2,3, Oonagh Shannon3
1Department of Biomedical Engineering, Lund University, Lund 222 42, Sweden.
Abstract:
Sepsis is a life-threatening condition caused by a dysregulated host response to an infection and is a leading cause of death worldwide. The condition is variable, which in combination with insufficient clinical markers, makes it challenging to predict when infection will progress to sepsis and to categorize patients into homogeneous patient subgroups. In this study, we demonstrate the use of acoustic trapping to rapidly enrich extracellular vesicles (EVs) from minute volumes of blood plasma from experimental mouse models of sepsis infected with the Gram-positive pathogen Streptococcus pyogenes or the Gram-negative pathogen Escherichia coli. Using quantitative mass spectrometry-based proteomics, we characterized the proteome of EVs and plasma to demonstrate that the EVs expand the observable proteome in plasma, with an emphasis on cellular processes and signaling. In our models, systemic bacterial infection altered the EV and plasma proteomes differently, with a predominant effect on proteins related to leukocyte migration in the EVs and on metabolism in the plasma. Finally, we show that E. coli infection significantly impacted metabolism, whereas S. pyogenes infection mainly affected the inflammatory response and neutrophil degranulation in our models. Collectively, our findings demonstrate that the acoustic trap facilitates access to plasma EVs, which in turn provides additional biological information which was not obtained from the plasma proteome alone.
Insights
Acoustic trapping isolates extracellular vesicles (EVs) from sepsis patient blood plasma, revealing distinct proteomic profiles. This method enhances understanding of infection-driven biological changes for improved sepsis diagnostics.
Area of Science:
- Biomedical Engineering
- Proteomics
- Sepsis Pathophysiology
Background:
- Sepsis is a life-threatening condition with variable presentation and insufficient clinical markers.
- Predicting sepsis progression and stratifying patients remains challenging.
- Extracellular vesicles (EVs) are emerging biomarkers, but their full potential in sepsis is underexplored.
Purpose of the Study:
- To utilize acoustic trapping for rapid enrichment of extracellular vesicles (EVs) from small plasma volumes in sepsis models.
- To characterize and compare the proteomes of EVs and plasma during bacterial infection.
- To investigate how different bacterial pathogens (Streptococcus pyogenes, Escherichia coli) impact EV and plasma proteomes.
Main Methods:
- Acoustic trapping for extracellular vesicle (EV) enrichment from mouse plasma.
- Quantitative mass spectrometry-based proteomics for proteome characterization.
- Comparative analysis of EV and plasma proteomes in sepsis models.
Main Results:
- Acoustic trapping efficiently enriched EVs, expanding the observable plasma proteome with focus on cellular processes and signaling.
- Systemic bacterial infection differentially altered EV and plasma proteomes.
- EVs were enriched in proteins related to leukocyte migration, while plasma proteins were linked to metabolism.
- Escherichia coli infection primarily impacted metabolism, whereas Streptococcus pyogenes infection affected inflammation and neutrophil degranulation.
Conclusions:
- Acoustic trapping provides access to plasma EVs, offering valuable biological insights beyond plasma proteome analysis alone.
- EV proteomic profiling in sepsis can differentiate responses to Gram-positive and Gram-negative bacterial infections.
- This approach holds promise for improved sepsis biomarker discovery and patient stratification.
