scholarly journals Fantastic voyage: the journey of intestinal microbiota-derived microvesicles through the body

2018 ◽  
Vol 46 (5) ◽  
pp. 1021-1027 ◽  
Author(s):  
Régis Stentz ◽  
Ana L. Carvalho ◽  
Emily J. Jones ◽  
Simon R. Carding
Keyword(s):  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
The Body ◽  
Gi Tract ◽  
Enzyme Degradation ◽  
Potential Applications ◽  
Delivery Vehicles ◽  
The Brain ◽  
Spherical Protrusions

As part of their life cycle, Gram-negative bacteria produce and release microvesicles (outer membrane vesicles, OMVs) consisting of spherical protrusions of the outer membrane that encapsulate periplasmic contents. OMVs produced by commensal bacteria in the gastrointestinal (GI) tract of animals are dispersed within the gut lumen with their cargo and enzymes being distributed across and throughout the GI tract. Their ultimate destination and fate is unclear although they can interact with and cross the intestinal epithelium using different entry pathways and access underlying immune cells in the lamina propria. OMVs have also been found in the bloodstream from which they can access various tissues and possibly the brain. The nanosize and non-replicative status of OMVs together with their resistance to enzyme degradation and low pH, alongside their ability to interact with the host, make them ideal candidates for delivering biologics to mucosal sites, such as the GI and the respiratory tract. In this mini-review, we discuss the fate of OMVs produced in the GI tract of animals with a focus on vesicles released by Bacteroides species and the use of OMVs as vaccine delivery vehicles and other potential applications.

scholarly journals Radiolabelled Bacterial Metallophores as Targeted PET Imaging Contrast Agents for Accurate Identification of Bacteria and Outer Membrane Vesicles in vivo

2020 ◽  
Author(s):  
Nabil A. Siddiqui ◽  
Hailey A. Houson ◽  
Shindu C. Thomas ◽  
Jose R. Blanco ◽  
Robert E. O’Donnell ◽  
...  
Keyword(s):  
Contrast Agents ◽  
Outer Membrane ◽  
Single Molecule ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
The Body ◽  
Taxonomic Resolution ◽  
Non Invasive ◽  
Bacterial Products

AbstractModern technologies such as 16s DNA sequencing capable of identifying microbes and provide taxonomic resolution at species and strain-specific levels is destined to be transformative1. Likewise, there is an emerging need to accurately identify both infectious and non-infectious microbes non-invasively in the body at the genus and species level to guide diagnosis and treatment strategies. Here, we report development of radiometal-labelled bacterial chelators, knowns as metallophores that allow non-invasive and selective imaging of bacteria and bacterial products in vivo. We show that these novel contrast agents are able to identify E. coli with strain level specificity and other bacteria, such as K. pneumoniae, based on expression of distinct cognate transporters on the bacterial surface. The probe is also capable of tracking probiotic, engineered bacteria and bacterial products, outer membrane vesicles (OMVs), in unique niches such as tumours. Moreover, we report that this novel targeted imaging approach has impactful applicability in monitoring antibiotic treatment outcomes in patients with pulmonary infections, thereby providing the ability to optimize individualized therapeutic approaches. Compared to traditional techniques used to manufacture probes, this strategy simplifies the process considerably by combining the function of metal attachment and cell recognition into a single molecule. Thus, we anticipate that these probes will be widely used in both clinical and investigative settings in living systems for non-invasive imaging of infectious and non-infectious organisms.

Bioengineered Bacterial Outer Membrane Vesicles as Cell-Specific Drug-Delivery Vehicles for Cancer Therapy

ACS Nano ◽  
2014 ◽  
Vol 8 (2) ◽  
pp. 1525-1537 ◽  
Author(s):  
Vipul Gujrati ◽  
Sunghyun Kim ◽  
Sang-Hyun Kim ◽  
Jung Joon Min ◽  
Hyon E Choy ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Specific Drug ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles ◽  
Bacterial Outer Membrane

scholarly journals Structural modifications of outer membrane vesicles to refine them as vaccine delivery vehicles

2009 ◽  
Vol 1788 (10) ◽  
pp. 2150-2159 ◽  
Author(s):  
Sang-Hyun Kim ◽  
Keun-Su Kim ◽  
Sang-Rae Lee ◽  
Ekyune Kim ◽  
Myeong-Su Kim ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Vaccine Delivery ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Structural Modifications ◽  
Delivery Vehicles

scholarly journals Porphyromonas gingivalis Outer Membrane Vesicles as the Major Driver of and Explanation for Neuropathogenesis, the Cholinergic Hypothesis, Iron Dyshomeostasis, and Salivary Lactoferrin in Alzheimer’s Disease

2021 ◽  
pp. 1-34
Author(s):  
Peter L. Nara ◽  
Daniel Sindelar ◽  
Marc S. Penn ◽  
Jan Potempa ◽  
W. Sue T. Griffin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Outer Membrane ◽  
Porphyromonas Gingivalis ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Direct Role ◽  
Cholinergic Hypothesis ◽  
Genetic Mechanisms ◽  
The Brain

Porphyromonas gingivalis (Pg) is a primary oral pathogen in the widespread biofilm-induced “chronic” multi-systems inflammatory disease(s) including Alzheimer’s disease (AD). It is possibly the only second identified unique example of a biological extremophile in the human body. Having a better understanding of the key microbiological and genetic mechanisms of its pathogenesis and disease induction are central to its future diagnosis, treatment, and possible prevention. The published literature around the role of Pg in AD highlights the bacteria’s direct role within the brain to cause disease. The available evidence, although somewhat adopted, does not fully support this as the major process. There are alternative pathogenic/virulence features associated with Pg that have been overlooked and may better explain the pathogenic processes found in the “infection hypothesis” of AD. A better explanation is offered here for the discrepancy in the relatively low amounts of “Pg bacteria” residing in the brain compared to the rather florid amounts and broad distribution of one or more of its major bacterial protein toxins. Related to this, the “Gingipains Hypothesis”, AD-related iron dyshomeostasis, and the early reduced salivary lactoferrin, along with the resurrection of the Cholinergic Hypothesis may now be integrated into one working model. The current paper suggests the highly evolved and developed Type IX secretory cargo system of Pg producing outer membrane vesicles may better explain the observed diseases. Thus it is hoped this paper can provide a unifying model for the sporadic form of AD and guide the direction of research, treatment, and possible prevention.

scholarly journals Bacterial Outer Membrane Vesicles as Antibiotic Delivery Vehicles

2021 ◽  
Vol 12 ◽  
Author(s):  
Shannon M. Collins ◽  
Angela C. Brown
Keyword(s):  
Outer Membrane ◽  
Cell Envelope ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Great Promise ◽  
Gram Negative ◽  
Delivery Vehicles ◽  
Bacterial Outer Membrane ◽  
Antibiotic Delivery

Bacterial outer membrane vesicles (OMVs) are nanometer-scale, spherical vehicles released by Gram-negative bacteria into their surroundings throughout growth. These OMVs have been demonstrated to play key roles in pathogenesis by delivering certain biomolecules to host cells, including toxins and other virulence factors. In addition, this biomolecular delivery function enables OMVs to facilitate intra-bacterial communication processes, such as quorum sensing and horizontal gene transfer. The unique ability of OMVs to deliver large biomolecules across the complex Gram-negative cell envelope has inspired the use of OMVs as antibiotic delivery vehicles to overcome transport limitations. In this review, we describe the advantages, applications, and biotechnological challenges of using OMVs as antibiotic delivery vehicles, studying both natural and engineered antibiotic applications of OMVs. We argue that OMVs hold great promise as antibiotic delivery vehicles, an urgently needed application to combat the growing threat of antibiotic resistance.

scholarly journals Characterization of Vibrio cholerae Outer Membrane Vesicles as a Candidate Vaccine for Cholera

2008 ◽  
Vol 77 (1) ◽  
pp. 472-484 ◽  
Author(s):  
Stefan Schild ◽  
Eric J. Nelson ◽  
Anne L. Bishop ◽  
Andrew Camilli
Keyword(s):  
Immune Response ◽  
Outer Membrane ◽  
Vibrio Cholerae ◽  
Stomach Contents ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Antigen Delivery ◽  
Heterologous Antigen ◽  
Adult Mice ◽  
Delivery Vehicles

ABSTRACT Outer membrane vesicles (OMVs) offer a new approach for an effective cholera vaccine. We recently demonstrated that immunization of female mice with OMVs induces a long-lasting immune response and results in protection of their neonatal offspring from Vibrio cholerae intestinal colonization. This study investigates the induced protective immunity observed after immunization with OMVs in more detail. Analysis of the stomach contents and sera of the neonates revealed significant amounts of anti-OMV immunoglobulins (Igs). Swapping of litters born to immunized and nonvaccinated control mice allowed us to distinguish between prenatal and neonatal uptakes of Igs. Transfer of Igs to neonates via milk was sufficient for complete protection of the neonates from colonization with V. cholerae, while prenatal transfer alone reduced colonization only. Detection of IgA and IgG1 in the fecal pellets of intranasally immunized adult mice indicates an induced immune response at the mucosal surface in the gastrointestinal tract, which is the site of colonization by V. cholerae. When a protocol with three intranasal immunizations 14 days apart was used, the OMVs proved to be efficacious at doses as low as 0.025 μg per immunization. This is almost equivalent to OMV concentrations found naturally in the supernatants of LB-grown cultures of V. cholerae. Heterologous expression of the periplasmic alkaline phosphatase (PhoA) of Escherichia coli resulted in the incorporation of PhoA into OMVs derived from V. cholerae. Intranasal immunization with OMVs loaded with PhoA induced a specific immune response against this heterologous antigen in mice. The detection of an immune response against this heterologously expressed protein is a promising step toward the potential use of OMVs as antigen delivery vehicles in vaccine design.

Electrophysiological Characterization of Transport Across Outer Membrane Channels from Gram-Negative Bacteria in Their Native Environment

2019 ◽  
Author(s):  
Jiajun Wang ◽  
Rémi Terrasse ◽  
Jayesh Arun Bafna ◽  
Lorraine Benier ◽  
Mathias Winterhalter
Keyword(s):  
Outer Membrane ◽  
Lipid Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Multi Drug Resistance ◽  
Gram Negative Bacteria ◽  
Membrane Channels ◽  
Gram Negative ◽  
Electrophysiological Characterization

Multi-drug resistance in Gram-negative bacteria is often associated with low permeability of the outer membrane. To investigate the role of membrane channels in the uptake of antibiotics, we extract, purify and reconstitute them into artificial planar membranes. To avoid this time-consuming procedure, here we show a robust approach using fusion of native outer membrane vesicles (OMV) into planar lipid bilayer which moreover allows also to some extend the characterization of membrane protein channels in their native environment. Two major membrane channels from <i>Escherichia coli</i>, OmpF and OmpC, were overexpressed from the host and the corresponding OMVs were collected. Each OMV fusion revealed surprisingly single or only few channel activities. The asymmetry of the OMV´s translates after fusion into the lipid membrane with the LPS dominantly present at the side of OMV addition. Compared to conventional reconstitution methods, the channels fused from OMVs containing LPS have similar conductance but a much broader distribution. The addition of Enrofloxacin on the LPS side yields somewhat higher association (<i>k<sub>on</sub></i>) and lower dissociation (<i>k<sub>off</sub></i>) rates compared to LPS-free reconstitution. We conclude that using outer membrane vesicles is a fast and easy approach for functional and structural studies of membrane channels in the native membrane.

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