School of Chemistry and Materials Science, Rochester Institute of Technology, Rochester, New York, USA.
Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, New York, USA.
J Biol Chem. 2022 Oct;298(10):102483. doi: 10.1016/j.jbc.2022.102483. Epub 2022 Sep 13.
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.
脓毒症是一种常危及生命的感染反应，当宿主促炎免疫反应异常升高和失调时发生。要诊断脓毒症，患者必须有明确或预测的感染，以及与脓毒症病理生理学相关的其他症状。然而，最近的一项研究发现，在大多数（70.1%）脓毒症病例中无法确定特定的致病生物，可能是由于使用了激进的抗生素或局部感染。患者脓毒症诊断的时间通常可以预测其临床结果，这凸显了需要更明确的分子诊断测试。在这里，我们概述了使用细菌外膜囊泡（OMVs）作为革兰氏阴性菌脓毒症诊断生物标志物的优势和挑战。优势包括 OMV 的丰度、在抗生素存在下的稳健性以及它们从亲代细胞中获得的独特特征，这可以允许区分细菌种类。挑战包括从复杂生物流体中分离 OMVs 所需的严格纯化方法，以及从具有与 OMVs 相似物理特性的类似大小的细胞外囊泡中分离 OMVs 的额外需求。
