Outer membrane vesicles as versatile tools for therapeutic approaches

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 spherical shaped facsimiles of the donor bacterium's surface with enclosed periplasmic content may serve multiple purposes for their host bacterium. This includes inter- and intra-species cell-cell communication, effector delivery to target cells and bacterial adaptation strategies. This review provides a concise overview on 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 non-living 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 might not only be suitable for biotechnological applications, but may also enable cell-specific delivery of designed therapeutics as they are efficiently internalized by non-professional 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 anti-cancer therapy.

Emerging role of microbiota derived outer membrane vesicles to preventive, therapeutic and diagnostic proposes

“…Currently, considerable investigations have been carried out to evaluate the role of OMVs in bacterial communication and infection development [ 186 , 187 ]. Besides, many groups have examined OMVs for their potential as delivery vehicles, bacterial vaccines, adjuvants cancer immunotherapy agents [ 22 , 28 , 188 – 190 ]. Nevertheless, there are some limitations, such as a lack of inadequate terminology, standardized methodology for the purification and/or isolation of different OMVs, and technical challenges in quantification and characterization [ 34 , 191 ].…”

A molecular toolkit for heterologous protein secretion across Bacteroides species

“…1B) . We suspect that the persistently high levels of BT_3382 are due to higher protein stability rather than continued production and secretion by B. theta during stationery growth as BT_3382 is reported to be enriched in OMVs 43 , which may lead to higher thermostability 44,45 .…”

Extracellular Vesicles of Probiotics: Shedding Light on the Biological Activity and Future Applications

“…Due to this, the electric charge of the EVs of probiotic bacteria can directly affect their colonization capacity of the host [ 31 , 39 , 45 ]. It seems to us that the low interest in this parameter among the scientific community can be explained by the willingness to administer to patients purified EVs of probiotics, without applying microorganisms secreting them (e.g., in a form of postbiotics) [ 46 ]. Although the influence of EVs on the colonization capacity of the probiotics producing them is not widely investigated, it should still be kept in mind that EVs applied in this way could affect the diversity and properties of the host microbiota [ 47 , 48 ].…”

“…Although the frequency in measuring quantity of probiotic EVs was quite low, the high homogeneity of applied research techniques allows for a relatively objective comparison of EVs’ production by different probiotics. In our opinion, the lack of universality in measuring the efficiency of production of probiotic EVs is, as stated before, associated with the frequent perception of these EVs as a therapeutic agent with designation to be administered in a purified form to patients (as postbiotics) and not necessarily as structures that would be secreted by the probiotic into the local environment, e.g., the intestines [ 46 ].…”