Transl Clin Pharmacol.  2018 Sep;26(3):103-110. 10.12793/tcp.2018.26.3.103.

Microbe-derived extracellular vesicles as a smart drug delivery system

• Yang J
• Kim EK
• McDowell A
• Kim YK

• KMID: 2420291
• DOI: http://doi.org/10.12793/tcp.2018.26.3.103

Abstract

The human microbiome is known to play an essential role in influencing host health. Extracellular vesicles (EVs) have also been reported to act on a variety of signaling pathways, distally transport cellular components such as proteins, lipids, and nucleic acid, and have immunomodulatory effects. Here we shall review the current understanding of the intersectionality of the human microbiome and EVs in the emerging field of microbiota-derived EVs and their pharmacological potential. Microbes secrete several classes of EVs: outer membrane vesicles (OMVs), membrane vesicles (MVs), and apoptotic bodies. EV biogenesis is unique to each cell and regulated by sophisticated signaling pathways. EVs are primarily composed of lipids, proteins, nucleic acids, and recent evidence suggests they may also carry metabolites. These components interact with host cells and control various cellular processes by transferring their constituents. The pharmacological potential of microbiomederived EVs as vaccine candidates, biomarkers, and a smart drug delivery system is a promising area of future research. Therefore, it is necessary to elucidate in detail the mechanisms of microbiome-derived EV action in host health in a multi-disciplinary manner.

Keyword

Drug delivery system; Extracellular vesicles; Microbiome; Pharmabiotics

MeSH Terms

Biomarkers
Drug Delivery Systems*
Extracellular Vesicles*
Membranes
Microbiota
Nucleic Acids
Biomarkers
Nucleic Acids

Figure

• 

  Figure 1 Proposed bacterial extracellular vesicle secretion. Bacteria ubiquitously release extracellular vesicles (EVs) into the extracellular milieu roughly 10-300 nm in diameter. EVs are composed of a lipid bilayer containing soluble and insoluble proteins, nucleic acids, and lipids. The lipid bilayer encasing the vesicular contents confers protection from extracellular degradation by nucleases and proteases, allowing distal transfer of EV cargo. (A) Gram negative and positive bacteria secrete ectosomes, or outer membrane vesicles (OMV) and membrane vesicles (MV), respectively. OMV biogenesis through budding of the outer membrane is well characterized, however the mechanism of MV biogenesis through the thick peptidoglycan cell wall of gram positive bacteria is not yet fully understood. (B) Bacterial cells also undergo apoptosis, a conserved self-destruct mechanism instigated by environmental stimuli such as quorum sensing or UV damage. After the apoptotic pathway is initiated, nucleoid DNA is degraded and subsequently fragmented, followed by cell membrane fragmentation. Finally, blebbing of the cell membrane occurs, resulting in release of bacterial apoptotic bodies containing bacterial cellular components.

• 

  Figure 2 Proposed bacterial extracellular vesicle composition and related function. Bacterial EVs are enclosed in a phospholipid bilayer originating from the bacterial membrane that along with lipo- and cytosolic proteins can be used as a nutrient source by targeted cells. Cytoplasmic proteins contained within the EV also have roles in immunomodulation and potential pharmacological applications. Lipoproteins and LPS embedded in the phospholipid bilayer moderate site-specific targeting of the EV for intra- and intercellular communication and EV constituent delivery. Nucleic acids including sRNA, mRNA, tRNA, rRNA, and DNA are transported in bacterial EVs, further contributing to immunomodulation as well as horizontal gene transfer. Recent evidence that bacterial EVs are metabolically active suggest that bacterial EV may also contain metabolites, increasing the pharmacological potential of bacterial EVs.

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