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Outer membrane vesicles as molecular biomarkers for Gram-negative sepsis: Taking advantage of nature's perfect
Lea Vacca Michel1, Thomas Gaborski2
1School of Chemistry and Materials Science, Rochester Institute of Technology, Rochester, New York, USA.
Abstract:
Sepsis is an often life-threatening response to infection, occurring when host proinflammatory immune responses become abnormally elevated and dysregulated. To diagnose sepsis, the patient must have a confirmed or predicted infection, as well as other symptoms associated with the pathophysiology of sepsis. However, a recent study found that a specific causal organism could not be determined in the majority (70.1%) of sepsis cases, likely due to aggressive antibiotics or localized infections. The timing of a patient's sepsis diagnosis is often predictive of their clinical outcome, underlining the need for a more definitive molecular diagnostic test. Here, we outline the advantages and challenges to using bacterial outer membrane vesicles (OMVs), nanoscale spherical buds derived from the outer membrane of Gram-negative bacteria, as a diagnostic biomarker for Gram-negative sepsis. Advantages include OMV abundance, their robustness in the presence of antibiotics, and their unique features derived from their parent cell that could allow for differentiation between bacterial species. Challenges include the rigorous purification methods required to isolate OMVs from complex biofluids and the additional need to separate OMVs from similarly sized extracellular vesicles, which can share physical properties with OMVs.
Insights
Bacterial outer membrane vesicles show promise as a diagnostic biomarker for Gram-negative sepsis. These vesicles are abundant, stable with antibiotics, and can identify specific bacteria, aiding in faster diagnosis.
Area of Science:
- Microbiology
- Immunology
- Biomarker Discovery
Background:
- Sepsis is a life-threatening immune response to infection.
- Current sepsis diagnosis relies on identifying infection and symptoms, but causative organisms are often undetermined (70.1%).
- Timely diagnosis is crucial for patient outcomes, highlighting the need for advanced molecular diagnostics.
Purpose of the Study:
- To evaluate bacterial outer membrane vesicles (OMVs) as a diagnostic biomarker for Gram-negative sepsis.
- To outline the advantages and challenges of using OMVs in sepsis diagnostics.
Main Methods:
- Review of existing literature on OMVs and their potential in sepsis diagnostics.
- Analysis of OMV characteristics, including abundance, stability, and species-specific features.
- Identification of challenges in OMV purification and differentiation from extracellular vesicles.
Main Results:
- OMVs are abundant and robust in the presence of antibiotics.
- OMVs possess unique features enabling differentiation between bacterial species.
- Purification of OMVs from biofluids and separation from extracellular vesicles present significant challenges.
Conclusions:
- Bacterial outer membrane vesicles offer a promising avenue for diagnosing Gram-negative sepsis.
- Further research is needed to overcome purification and separation challenges for clinical application.
- OMVs could lead to more definitive and timely sepsis diagnoses.
