Gram-Negative Bacteria-derived Exosome Research and Applications

Gram-negative bacteria exosomes come from a wide range of sources and are increasingly being researched and characterized. Benefiting from carrying specific bacterial antigens, they not only interact with immune cells as potential therapeutic immune adjuvants or targeting vectors, but can also be genetically engineered to perform functional modifications, thus laying the groundwork for their application as nanovaccine delivery platforms. Creative Biolabs has accumulated research insights on a wide range of gram-negative bacterial-derived exosomes, and can provide one-stop research services for gram-negative bacteria-derived exosomes.

Features of Gram-negative Bacterial-derived Outer Membrane Vesicles

Exosome-like vesicles of gram-negative bacterial origin are secreted from the bacterial periplasm and contain components such as phospholipids, lipopolysaccharides, outer membrane proteins, and gram-negative bacterial-specific antigens.
Capable of transporting biochemicals from donor Gram-negative bacteria over long distances into target cells, minimizing cargo from being diluted and degraded.
Gram-negative bacterial-derived exosomes carry the endotoxin lipopolysaccharide as a characteristic component that transmits cytotoxicity.
With a nano-hollow structure and highly immunogenic, they effectively activate the host immune system.

Fig. 1 Typical composition of gram-negative bacteria-derived vesicles.¹

Research on Multiple Gram-negative Bacteria-derived Exosomes

Gram-negative Bacterial-derived Exosome Type	Research
Bacteroides vulgatus-derived Exosome	Results of MHC-II, expression of synergistic proteins, and inflammatory cytokine assays in immune cells indicated that Bacteroides vulgatus-derived exosomes carrying ligands for TLR4 and TLR2 were able to induce silencing of the immune response, demonstrating the potential of Bacteroides vulgatus-derived vesicles as tools for intervening in inflammatory diseases.
Moraxella catarrhalis-derived exosome	Moraxella catarrhalis-derived exosomes were revealed by time-kill assay to favor yeast antimicrobial drug activity for normal growth. Moreover, Moraxella catarrhalis-derived exosomes triggered the host inflammatory response due to the activation of the human beta-defensin-2 promoter under the regulation of IL-1β, which induced neutrophils chemotaxis to the respiratory system and releasing neutrophil granules containing inflammatory mediators.
Haemophilus influenzae-derived Exosome	Haemophilus influenzae-derived exosomes were capable of carrying suitable adjuvants as vaccine candidates to stimulate immune responses and induce high levels of antibody production in mice. Upon receiving another antigenic attack, the immunized mice were found to release cytokines that regulate immune-related cytokines, such as IFN-γ, as well as anti-inflammatory factors.
Acinetobacter baumannii-derived Exosome	It was demonstrated that Acinetobacter baumannii-derived exosomes induced a significant humoral immune response in mice infected with specific antigens. Moreover, intranasal administration induced IgA production in specific mucosal immunity and reduced bacterial transmission, showing a better protective effect than subcutaneous and intramuscular administration.
Helicobacter pylori-derived Exosome	Helicobacter pylori-derived exosomes were shown to be able to invade gastric epithelial cells, mediating infection and pathogenesis of Helicobacter pylori. Their harboring of the CagA protein is involved in the toxin action in target cells. In addition, Helicobacter pylori-derived exosome contains a variety of immunologically active protein components, including Hop family outer membrane proteins, urease subunit B, and vacuolating cytotoxin-associated proteins, and has been demonstrated to have the ability to prevent and control Helicobacter pylori infection in animal studies.
Porphyromonas gingivalis-derived Exosome	Porphyromonas gingivalis-derived exosomes were identified as capable of causing gingipain-dependent cellular damage to oral epithelial cells or gingival fibroblasts. The presence of all protobacterial adhesion molecules in their lumen, such as protofibrillar proteins, gingivins, and hemagglutinins, can mediate interactions between oral bacteria involved in plaque diversity and periodontitis-associated diseases.
Bordetella pertussis-derived Exosome	Exosome-like vesicles isolated from Bordetella pertussis were encapsulated in sodium alginate nanoparticles to construct a drug slow-release system. Mice treated with this bacterial vesicle-based drug showed higher immune indices and significantly secreted immune-related factors such as antibodies, IL-17, and IL-10.
Burkholderia thailandensisx-derived Exosome	Burkholderia thailandensis-derived exosomes were observed to exert significant protection through stimulation of the innate immune response against melioidosis pneumonia induced by their donor organisms in animal tests, and were found to be coated with a variety of antimicrobial compounds, such as rhamnolipids and peptidoglycan hydrolases, in their lumen.
Pseudomonas aeruginosa-derived Exosome	Assays of corneal epithelial cells and neutrophils revealed that Pseudomonas aeruginosa-derived exosomes on the one hand favored their parent bacterium survival and release of pro-inflammatory cytokines in cells, and on the other hand contributed to the neutrophil chemotaxis and subsequent respiratory bursts.
Klebsiella pneumonia-derived Exosome	Klebsiella pneumonia-derived exosomes encapsulating chemotherapeutic agents have been revealed in tumor cell models and hormonal mouse models to not only improve the pharmacokinetics of chemotherapeutic agents to deliver antitumor effects, but also synergize the antitumor effect by recruiting macrophages to accumulate in tumor tissues with their own immunogenicity.
Escherichia coli-derived Exosome	Escherichia coli-derived Exosomes were discovered to inhibit autophagy-lysosome fusion and autophagosome clearance as well as to activate the noncanonical inflammasome pathway in a dose-dependent manner relying on the parent bacterium's expressing the virulence factor HlyF. In contrast, exosomes isolated from Escherichia coli with mutations in the virulence factor HlyF failed to induce this autophagy blockade.
Salmonella typhimurium-derived Exosome	Salmonella typhimurium-derived exosomes were modified with recombinant receptor-binding domains against the virus, which were detected to induce the specific plasma antibodies and mucosal antibodies production in the vaccinated hamsters. After the corresponding viral attack, the Salmonella typhimurium-derived exosome vaccine protected the hamsters with evoking the specific antibodies produced in a neutralizing response to the virus, thus alleviating the pathology.
Neisseria meningitidis-derived Exosome	Exosomes were isolated from a modified Neisseria meningitidis strain deficient in major outer membrane proteins, which immunized mouse models of lower genital tract infections were found to produce specific antibodies recognizing a wider range of gonococcal antigens and to provide faster and stronger resistance to gonococcal attack.
Neisseria lactamica-derived Exosome	It has been investigated to biotinylate Neisseria lactamica-derived exosomes and then achieve coupling of the target antigen on exosomes based on the high-affinity binding between rhizavidin and biotin. These engineered Neisseria lactamica-derived exosomes are capable of antigen presentation and significantly increase organismal antigen recognition and trigger stronger immune responses.

Gram-negative bacteria-derived outer membrane vesicles have the ability to cross the mucus layer to participate in the regulation of host nutrient metabolism and physiology, displaying exosome-like properties. Creative Biolabs provides research services related to Gram-negative bacteria-derived exosomes to help clients expand their insights into Gram-negative bacteria-derived exosomes and their interactions with the host. Please contact us to learn more.

Reference

Dell'Annunziata, Federica, et al. "Gene transfer potential of outer membrane vesicles of gram-negative bacteria." International journal of molecular sciences 22.11 (2021): 5985.

Plant Exosome Isolation