Outer Membrane Vesicle-Host Cell Interactions

Cecil, Jessica D.; Sirisaengtaksin, Natalie; O'Brien-Simpson, Neil M; Krachler, Anne Marie

doi:10.1128/microbiolspec.psib-0001-2018

Cited by 125 publications

(97 citation statements)

References 124 publications

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“…Bacterial OMVs normally produced by Gram-negative bacteria are increasingly being recognized as a secretory inter-and intra-kingdom communication system (Jan, 2017;Cecil et al, 2019). However, many features of this mechanism remain to be defined (Margolis and Sadovsky, 2019).…”

Section: Discussionmentioning

confidence: 99%

The Uptake, Trafficking, and Biodistribution of Bacteroides thetaiotaomicron Generated Outer Membrane Vesicles

et al. 2020

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Gram-negative bacteria ubiquitously produce and release nano-size, non-replicative outer membrane vesicles (OMVs). In the gastrointestinal (GI-) tract, OMVs generated by members of the intestinal microbiota are believed to contribute to maintaining the intestinal microbial ecosystem and mediating bacteria-host interactions, including the delivery of bacterial effector molecules to host cells to modulate their physiology. Bacterial OMVs have also been found in the bloodstream although their origin and fate are unclear. Here we have investigated the interactions between OMVs produced by the major human gut commensal bacterium, Bacteroides thetaiotaomicron (Bt), with cells of the GI-tract. Using a combination of in vitro culture systems including intestinal epithelial organoids and in vivo imaging we show that intestinal epithelial cells principally acquire Bt OMVs via dynamin-dependent endocytosis followed by intracellular trafficking to LAMP-1 expressing endo-lysosomal vesicles and co-localization with the perinuclear membrane. We observed that Bt OMVs can also transmigrate through epithelial cells via a paracellular route with in vivo imaging demonstrating that within hours of oral administration Bt OMVs can be detected in systemic tissues and in particular, the liver. Our findings raise the intriguing possibility that OMVs may act as a long-distance microbiota-host communication system.

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Section: Discussionmentioning

confidence: 99%

The Uptake, Trafficking, and Biodistribution of Bacteroides thetaiotaomicron Generated Outer Membrane Vesicles

et al. 2020

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“…Therefore, to develop a safe, universal, effective, and low-cost vaccine is a key priority. OMVs are naturally nonreplicating, highly immunogenic spherical nanoparticles derived from Gram-negative bacteria (Ho et al, 2015;Cecil et al, 2019). As OMVs from pathogenic bacteria have been successfully used as vaccines (Gerritzen et al, 2017), there is interest in the OMVs of A. paragallinarum as potential vaccine candidates.…”

Section: Discussionmentioning

confidence: 99%

Component Identification and Functional Analysis of Outer Membrane Vesicles Released by Avibacterium paragallinarum

et al. 2020

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Avibacterium paragallinarum, the causative agent of infectious coryza, is known to release outer membrane vesicles (OMVs). In the present study, we investigated the composition, bioactivities, and functional properties of the OMVs of A. paragallinarum. Following extraction and purification, the OMVs were observed to be spherical in shape, with diameters ranging from 20 to 300 nm. The vesicles contained endotoxin as well as genomic DNA. The molecular weights of the OMV-contained protein fragments were mostly concentrated at 65 and 15 kDa. The components of the OMV proteins were mainly various functional enzymes (e.g., ATP-dependent RNA helicase), structural components (e.g., streptomycin B receptor and membrane protein), and some hypothetical proteins with unknown functions. The expression levels of inflammation-related factors, such as interleukin (IL)-2, IL-6, IL-1β, IL-10, and inducible nitric oxide synthase (iNOs), were significantly upregulated in chicken macrophage cells HD11 incubated with OMVs. Serum IgG antibodies were measured after two intramuscular injections of an OMV-based vaccine into specific pathogen-free (SPF) chickens. The vaccinated chickens were then challenged by A. paragallinarum of homologous and heterologous serovars. It was noted that the vaccinated chickens produced immunoglobulin G (IgG) antibodies against A. paragallinarum. The OMVs conferred an acceptable level of protection (70%), defined as an absence of colonization and of clinical signs, against the homologous strain (serovar A), while the cross-protection against heterologous challenge with serovars B and C was much weaker. However, the OMVS did provide significant protection against clinical signs for all three serovars. Overall, this study laid a foundation for further unraveling the functional roles of OMVs released by A. paragallinarum.

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“…OMV release following sex steroid exposure represents an underappreciated and important bacterial virulence mechanism (28,43). With a central role in cell communication, OMVs are key to biofilm formation and facilitating host-pathogen interactions, which is attributed to their proinflammatory properties (44)(45)(46). A defensive role has also been proposed, where OMVs inhibit the efficacy of antimicrobial agents that target the bacterial cell wall (24).…”

Section: Discussionmentioning

confidence: 99%

Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa

Vidaillac

Yong

Aschtgen

et al. 2020

mBio

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Estrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid Pseudomonas aeruginosa in the airways of patients with chronic respiratory diseases, including cystic fibrosis. This results in long-term persistence, poorer clinical outcomes, and limited therapeutic options. In this study, we demonstrate that at physiological concentrations, sex steroids, including testosterone and estriol, induce membrane stress responses in P. aeruginosa. This is characterized by increased virulence and consequent inflammation and release of proinflammatory outer membrane vesicles promoting in vivo persistence of the bacteria. The steroid-induced P. aeruginosa response correlates with the molecular polarity of the hormones and membrane fluidic properties of the bacteria. This novel mechanism of interaction between sex steroids and P. aeruginosa explicates the reported increased disease severity observed in females with cystic fibrosis and provides evidence for the therapeutic potential of the modulation of sex steroids to achieve better clinical outcomes in patients with hormone-responsive strains. IMPORTANCE Molecular mechanisms by which sex steroids interact with P. aeruginosa to modulate its virulence have yet to be reported. Our work provides the first characterization of a steroid-induced membrane stress mechanism promoting P. aeruginosa virulence, which includes the release of proinflammatory outer membrane vesicles, resulting in inflammation, host tissue damage, and reduced bacterial clearance. We further demonstrate that at nanomolar (physiological) concentrations, male and female sex steroids promote virulence in clinical strains of P. aeruginosa based on their dynamic membrane fluidic properties. This work provides, for the first-time, mechanistic insight to better understand and predict the P. aeruginosa related response to sex steroids and explain the interindividual patient variability observed in respiratory diseases such as cystic fibrosis that are complicated by gender differences and chronic P. aeruginosa infection.

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Outer Membrane Vesicle-Host Cell Interactions

Cited by 125 publications

References 124 publications

The Uptake, Trafficking, and Biodistribution of Bacteroides thetaiotaomicron Generated Outer Membrane Vesicles

The Uptake, Trafficking, and Biodistribution of Bacteroides thetaiotaomicron Generated Outer Membrane Vesicles

Component Identification and Functional Analysis of Outer Membrane Vesicles Released by Avibacterium paragallinarum

Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa

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