Extracellular vesicles as novel assay tools to study cellular interactions of anti-infective compounds – A perspective

Richter, Robert; Lehr, Claus‐Michael

doi:10.1016/j.addr.2021.04.010

Cited by 6 publications

(11 citation statements)

References 165 publications

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“…Exosomes are multi-vesicular endosomes that originate from the endocytic system and are formed through four processes: outgrowth, invagination, multivesicular body formation and secretion, and are spherical, flat or cup-shaped vesicles with a diameter of 30–150 nm ( Spilak et al, 2021 ; Staubach et al, 2021 ; Sun et al, 2021 ). In recent years, it has been found that exosomes are distributed in human body fluids, including blood, urine, saliva, thoracoabdominal fluid, cerebrospinal fluid, bile, milk, tears and semen ( Yu et al, 2021a ; Zhang et al, 2021b ; Lin et al, 2021 ; Mohammadi et al, 2021 ; Richter and Lehr, 2021 ). In addition, exosomes of different tissue sources carry different nucleic acids, proteins and lipids ( Teng and Fussenegger, 2020 ; Shehzad et al, 2021 ; Wu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Advances in the Application of Exosomes Identification Using Surface-Enhanced Raman Spectroscopy for the Early Detection of Cancers

Yang

Jia

2022

Front. Bioeng. Biotechnol.

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Exosomes are small nanoscale vesicles with a double-layered lipid membrane structure secreted by cells, and almost all types of cells can secrete exosomes. Exosomes carry a variety of biologically active contents such as nucleic acids and proteins, and play an important role not only in intercellular information exchange and signal transduction, but also in various pathophysiological processes in the human body. Surface-enhanced Raman Spectroscopy (SERS) uses light to interact with nanostructured materials such as gold and silver to produce a strong surface plasmon resonance effect, which can significantly enhance the Raman signal of molecules adsorbed on the surface of nanostructures to obtain a rich fingerprint of the sample itself or Raman probe molecules with ultra-sensitivity. The unique advantages of SERS, such as non-invasive and high sensitivity, good selectivity, fast analysis speed, and low water interference, make it a promising technology for life science and clinical testing applications. In this paper, we briefly introduce exosomes and the current main detection methods. We also describe the basic principles of SERS and the progress of the application of unlabeled and labeled SERS in exosome detection. This paper also summarizes the value of SERS-based exosome assays for early tumor diagnosis.

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Section: Introductionmentioning

confidence: 99%

Advances in the Application of Exosomes Identification Using Surface-Enhanced Raman Spectroscopy for the Early Detection of Cancers

Yang

Jia

2022

Front. Bioeng. Biotechnol.

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“…OMVs can be considered to some degree as naturally derived proteoliposomes, but with higher complexity regarding their structure and content. [ 21,36 ]…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…This would make such assays even more useful in early anti-Gram-negative drug development, especially in the phase of lead identification and lead optimization. [21] Extracellular vesicles (EV) are a biomaterial constitutively shed by virtually all cells to their environment. [22] Although their concept can be even traced back as far as to Charles Darwin, [23] these spherical membrane structures have only recently become a popular focus of research related to diagnosis, [24,25] cellular behavior and interaction, [26,27] pathogen virulence as well as drug delivery.…”

Section: Introductionmentioning

confidence: 99%

“…[22] Although their concept can be even traced back as far as to Charles Darwin, [23] these spherical membrane structures have only recently become a popular focus of research related to diagnosis, [24,25] cellular behavior and interaction, [26,27] pathogen virulence as well as drug delivery. [21,28,29] Depending on their origin and composition, EVs fulfill different purposes, such as cell-to-cell communication, transfer of resistance genes as well as virulence factors and defense, [30] Outer membrane vesicles (OMVs) are one type of EVs, which originate from the OM of Gram-negative bacteria and provide them with unique characteristics. One important feature is the presence of OM proteins, of which porins -protein channels of the OM, allowing for a selective translocation into the Gramnegative bacterial cell -proved to significantly rule overall bacterial bioavailability and eventually antibiotic activity of small polar molecules.…”

Section: Introductionmentioning

confidence: 99%

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An Outer Membrane Vesicle‐Based Permeation Assay (OMPA) for Assessing Bacterial Bioavailability

Richter

Kamal

Koch

et al. 2021

Adv Healthcare Materials

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When searching for new antibiotics against Gram-negative bacterial infections, a better understanding of the permeability across the cell envelope and tools to discriminate high from low bacterial bioavailability compounds are urgently needed. Inspired by the phospholipid vesicle-based permeation assay (PVPA), which is designed to predict non-facilitated permeation across phospholipid membranes, outer membrane vesicles (OMVs) of Escherichia coli either enriched or deficient of porins are employed to coat filter supports for predicting drug uptake across the complex cell envelope. OMVs and the obtained in vitro model are structurally and functionally characterized using cryo-TEM, SEM, CLSM, SAXS, and light scattering techniques. In vitro permeability, obtained from the membrane model for a set of nine antibiotics, correlates with reported in bacterio accumulation data and allows to discriminate high from low accumulating antibiotics. In contrast, the correlation of the same data set generated by liposome-based comparator membranes is poor. This better correlation of the OMV-derived membranes points to the importance of hydrophilic membrane components, such as lipopolysaccharides and porins, since those features are lacking in liposomal comparator membranes. This approach can offer in the future a high throughput screening tool with high predictive capacity or can help to identify compound-and bacteria-specific passive uptake pathways.

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Yields and Immunomodulatory Effects of Pneumococcal Membrane Vesicles Differ with the Bacterial Growth Phase

Mehanny

Kroniger

Koch

et al. 2021

Adv Healthcare Materials

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Streptococcus pneumoniae infections are a leading cause of death worldwide. Bacterial membrane vesicles (MVs) are promising vaccine candidates because of the antigenic components of their parent microorganisms. Pneumococcal MVs exhibit low toxicity towards several cell lines, but their clinical translation requires a high yield and strong immunogenic effects without compromising immune cell viability. MVs are isolated during either the stationary phase (24 h) or death phase (48 h), and their yields, immunogenicity and cytotoxicity in human primary macrophages and dendritic cells have been investigated. Death-phase vesicles showed higher yields than stationary-phase vesicles. Both vesicle types displayed acceptable compatibility with primary immune cells and several cell lines. Both vesicle types showed comparable uptake and enhanced release of the inflammatory cytokines, tumor necrosis factor and interleukin-6, from human primary immune cells. Proteomic analysis revealed similarities in vesicular immunogenic proteins such as pneumolysin, pneumococcal surface protein A, and IgA1 protease in both vesicle types, but stationary-phase MVs showed significantly lower autolysin levels than death-phase MVs. Although death-phase vesicles produced higher yields, they lacked superiority to stationary-phase vesicles as vaccine candidates owing to their similar antigenic protein cargo and comparable uptake into primary human immune cells.

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Extracellular vesicles as novel assay tools to study cellular interactions of anti-infective compounds – A perspective

Cited by 6 publications

References 165 publications

Advances in the Application of Exosomes Identification Using Surface-Enhanced Raman Spectroscopy for the Early Detection of Cancers

Advances in the Application of Exosomes Identification Using Surface-Enhanced Raman Spectroscopy for the Early Detection of Cancers

An Outer Membrane Vesicle‐Based Permeation Assay (OMPA) for Assessing Bacterial Bioavailability

Yields and Immunomodulatory Effects of Pneumococcal Membrane Vesicles Differ with the Bacterial Growth Phase

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