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Outer membrane vesicles as versatile tools for therapeutic approaches - PubMed

  • ️Fri Jan 01 2021

Outer membrane vesicles as versatile tools for therapeutic approaches

Franz G Zingl et al. Microlife. 2021.

Abstract

Budding of the bacterial surface results in the formation and secretion of outer membrane vesicles, which is a conserved phenomenon observed in Gram-negative bacteria. Recent studies highlight that these sphere-shaped facsimiles of the donor bacterium's surface with enclosed periplasmic content may serve multiple purposes for their host bacterium. These include inter- and intraspecies cell-cell communication, effector delivery to target cells and bacterial adaptation strategies. This review provides a concise overview of potential medical applications to exploit outer membrane vesicles for therapeutic approaches. Due to the fact that outer membrane vesicles resemble the surface of their donor cells, they represent interesting nonliving candidates for vaccine development. Furthermore, bacterial donor species can be genetically engineered to display various proteins and glycans of interest on the outer membrane vesicle surface or in their lumen. Outer membrane vesicles also possess valuable bioreactor features as they have the natural capacity to protect, stabilize and enhance the activity of luminal enzymes. Along these features, outer membrane vesicles not only might be suitable for biotechnological applications but may also enable cell-specific delivery of designed therapeutics as they are efficiently internalized by nonprofessional phagocytes. Finally, outer membrane vesicles are potent modulators of our immune system with pro- and anti-inflammatory properties. A deeper understanding of immunoregulatory effects provoked by different outer membrane vesicles is the basis for their possible future applications ranging from inflammation and immune response modulation to anticancer therapy.

Keywords: OMV; bacterial vesicles; host cell interaction; immunomodulation; inflammation; vaccine development.

© The Author(s) 2021. Published by Oxford University Press on behalf of FEMS.

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Conflict of interest statement

None declared.

Figures

Figure 1.
Figure 1.

Overview of the therapeutic potential of OMVs. OMVs are released from bacterial cells (green or blue) with natural luminal content (gray). OMVs are recognized by host cell receptors (yellow), i.e. extracellularly via TLRs and in the cytosol after internalization via PRRs, resulting in inflammatory and humoral immune responses. Thus, OMVs could be used to specifically modulate pro- and anti-inflammatory responses. Moreover, OMVs can be used as vaccine candidates derived from an individual bacterial species (green or blue OMVs), derived from multiple species and used as mixtures (green and blue OMVs) or derived from genetically engineered to display heterologously expressed antigens (green OMVs with heterologously expressed antigens in red). Genetic engineering of donor bacterial cells also allows to modulate the composition of OMVs to decorate or load OMVs with heterologously expressed biomolecules (red components in or on OMVs). Applications of such bioengineered OMVs range from biocatalysis and biodegradation to delivery of natural and heterologously effectors to host cells, including targeting of specific host cell types via defined receptor interactions (purple).

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