(C) Superimposition of apo FpvA and FpvApyoverdineiron. This hypervesiculation might have an important Many groups have selected ClyA from E. coli as the fusion partner to deliver exogenous proteins to OMVs (31, 55, 143). FOIA National Library of Medicine
Physical properties of the bacterial outer membrane Fbrega MJ, Aguilera L, Gimnez R, Varela E, Alexandra Caas M, et al. 2019. In this review, we discuss the multiple roles of OMVs and the current knowledge of OMV biogenesis. 7:10515), (A) Protein Delivery. 2015. Rev. author and source are acknowledged. Reproduced with permission from reference 60. It is composed of three covalently linked moieties: lipid A, core, and O-sidechains. sharing sensitive information, make sure youre on a federal After OMVs have bound to lipid rafts, they are internalized through one of many endocytic pathways (19, 53, 86, 116). These challenges include increasing the vesicle yield, reducing the immunogenicity of the OMVs, incorporating specific molecules, and promoting targeting of specific cell types. Cancers (Basel). Lderitz O, Freudenberg MA, Galanos C, Lehmann V, Rietschel ET, Shaw DH. Up to four bacterial antigens were tethered to the surface of OMVs using the hemoglobin protease (Hbp). The first evidence of DNA in OMVs was uncovered in 1995, when Kadurugamuwa and Beveridge observed its presence in the OMVs produced by two strains of P. aeruginosa (H103 and ATCC 19660) (32). sensing molecules) over stress response and biofilm formation to associated with vesicles than in their soluble form. Both the unique and repeat regions of the Porphyromonas gingivalis hemagglutin A are involved in adhesion and invasion of host cells. In another example, the Francisella tularensis O-antigen polysaccharide gene cluster was also successfully expressed in E. coli to produce glycoengineered OMVs decorated with F. tularensis O-antigen (32). Exp Cell Res. Zhang Y, Fang Z, Li R, Huang X, Liu Q. The vesicle contains outer membrane-associated proteins and lipids (including lipopolysaccharide), as well as periplasmic components such as peptidoglycan. Bielaszewska M, Rter C, Kunsmann L, Greune L, Bauwens A, et al. 2020 Jul 10;323:253-268. doi: 10.1016/j.jconrel.2020.04.031. and transmitted securely. Bacterial outer membrane vesicles as a platform for biomedical applications: An update. Alternatively, the interaction could be mediated by a yet unknown sorting factor, which would recruit the protein to the O-antigen-enriched region in the OMV. (C) Structure of the plug domains with the signaling domain for FpvA (side view). In some cases, this new gene is expressed by daughter cells. One strategy to reduce the toxicity of LPS is to genetically modify the genes leading to full acylation of the lipid A moiety. also represents the first general mechanism of OMV formation applicable to all Here, we address several biogenesis mechanisms proposed to explain how OMVs are formed (Figure 2). Prokaryotic membrane vesicles: new insights on biogenesis and biological roles. In contrast to other acid-fast bacterial porins, it shows sequence similarity to OMP (OmpA) homologues from Gram-negative bacteria. Similarly, OMV-mediated horizontal gene transfer has also been identified in the oral pathogen Porphyromonas gingivalis (36), E. coli O104:H4 (37), and S. typhi (38). Smaller OMVs preferentially enter epithelial cells via caveola-mediated endocytosis (137). Before (E) OMVs can be used as an mRNA delivery platform to activate strong anti-tumor immune responses. Indeed, intense research on that topic revealed that Furthermore, OMV cargo varies between strains, which may in some cases limit their applicability to a specific subset of strains. Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants, An ABC transport system that maintains lipid asymmetry in the gram-negative outer membrane. One of the earliest models for OMV formation linked OMV biogenesis to a decrease in OMpeptidoglycan cross-links at the site of vesicle formation (Figure 2b). Daleke-Schermerhorn Maria H, Felix T, Soprova Z, ten Hagen-Jongman Corinne M, Vikstrm D, Majlessi L, et al.. Decoration of Outer Membrane Vesicles With Multiple Antigens by Using an Autotransporter Approach, Engineering Multi-Functional Bacterial Outer Membrane Vesicles as Modular Nanodevices for Biosensing and Bioimaging. Gram-negative bacteria actively secrete outer membrane vesicles, spherical nano-meter-sized proteolipids enriched with outer membrane proteins, to the surroundings. Once the dip has been completed, the wafer should be moved down into the backing plate (therefore, it is important that the wafer is also aligned with the position of the backing plate). As PQS is found at high concentrations in OMVs, the fusion of a single vesicle with a bacterial cell is enough to trigger the quorum sensing response. No use, distribution or reproduction is permitted which does not comply with these terms. Elhenawy W, Bording-Jorgensen M, Valguarnera E, Haurat MF, Wine E, Feldman MF. (Fanucci, Lee, and Cafiso 2003) suggest that the conformation of this small domain may be very sensitive to its environment, and to solutes used during crystallization (Freed, Horanyi, Wiener, & Cafiso 2010). Slow transport through porins needs to be considered when designing novel drugs against mycobacterial diseases. Many concerns stem from the fact that despite more than 50 years of research, we have yet to elucidate the mechanism(s) for their formation. The innate immune system of plants recognizes and responds to purified OMVs from plant pathogens (7). In addition, the structures have been solved of these TBDTs in various loading states, and for two of them bound to the periplasmic domain of TonB (FhuA and BtuB, the ferrichrome and vitamin B12 TBDTs in E. coli, respectively; Table 1). In a mouse model of ETEC infection, the levofloxacin-containing OMVs were more effective than free drug. Gram-negative bacteria. Another porin, MspA, is the main porin of the related, fast-growing, nonpathogenic species M. smegmatis. This site needs JavaScript to work properly. This mechanism appears to be limited to P. aeruginosa and related species that produce PQS (71). 2018. Bitto NJ, Chapman R, Pidot S, Costin A, Lo C, Choi J, et al.. Bacterial Membrane Vesicles Transport Their DNA Cargo Into Host Cells. Analysis of OM and OMV fractions from different microorganisms revealed a distinct enrichment of proteins and lipids in each fraction (1, 45, 63, 66, 72, 78, 93, 105, 121, 131).
Bacterial Outer Membrane Vesicles: From Discovery to This mechanism might reduced in PL transporter mutant OMVs, suggesting that defined PL rearrangements promote Some TBDTs have an additional N-terminal domain, upstream from the plug domain and called the signaling domain. The pyoverdineiron complexes are displayed in van der Waals spheres (A) Side view of apo FpvA. Given recent technical advances in mass spectrometry and microscopy, it will be possible to investigate the vesiculation process in relevant clinical strains and in infection models to decipher OMV biogenesis mechanisms and establish their true biological significance. Immunization with Salmonella enterica serovar Typhimurium-derived outer membrane vesicles delivering the pneumococcal protein PspA confers protection against challenge with Streptococcus pneumoniae. Epub 2020 Apr 22. Alaniz RC, Deatherage BL, Lara JC, Cookson BT. Unfortunately, these vaccines have had an overwhelmingly low rate of efficacy (less than 5%) (148). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. As the silicon wafer moves through the monolayer during the Schaefer dip, a jump in surface pressure will occur with the magnitude of the jump depending on composition and surface pressure of the monolayer. Sol M, Scheibner F, Hoffmeister A-K, Hartmann N, Hause G, et al. Besides its possible impact on bacterial physiology and pathogenesis, our proposed new Deatherage BL, Lara JC, Bergsbaken T, Rassoulian Barrett SL, Lara S, Cookson BT. (A) OMVs facilitate immune-mediated tumor clearance after photothermal therapy through orchestrating antigen capture and immune modulation. M.A. The functional RNA cargo of bacterial membrane vesicles. Turner L, Bitto NJ, Steer DL, Lo C, DCosta K, et al. mBio. 2016. Although detailed mechanisms of this process remain elusive, future work to better understand this delivery processes will further enhance research into the use of OMVs as antibiotic delivery vehicles to overcome current transport limitations. Thus, this class of proteins still contains surprises. No OMVs were able to lyse cells of the parent strain (19). Evans AGL, Davey HM, Cookson A, Currinn H, Cooke-Fox G, Stanczyk PJ, et al.. Fulsundar S, Harms K, Flaten GE, Johnsen PJ, Chopade BA, Nielsen KM. Li etal. significantly decreased during the initial stages of nasopharyngeal colonization, we These results suggest that electroporation is an effective method for loading a variety of cargo into the OMV lumen, and could have great potential for improving the encapsulation efficiencies of antibiotics. Escherichia coli tol-pal mutants form outer membrane vesicles. This TonB box is necessary for TBDTs to become active: it is required for siderophoreiron complex transport from the extracellular medium into the periplasm and, for TBDTs of group 2, for activation of the signaling cascade (Shirley & Lamont, 2009). Furthermore, while some work has demonstrated stability of OMVs under certain storage conditions (63), additional research to identify and/or develop optimal processing and storage conditions that do not affect OMV integrity are necessary. (d) The VacJ/Yrb ABC transporter is involved in retrograde transport of phospholipids from the OM. PagL is tightly regulated and is expressed inside macrophages (112). Biogenesis of the type 1 pilus fiber in Escherichia coli requires the product of the fimC locus. Microbiota and Extracellular Vesicles in Anti-PD-1/PD-L1 Therapy. Liang X, Dai N, Sheng K, Lu H, Wang J, Chen L, Wang Y. Contrary to LPS in P. aeruginosa, both LPS types are packed into P. gingivalis OMVs (66). coli are preferably transported via OMVs. HHS Vulnerability Disclosure, Help Bookshelf 2016. ferric uptake regulator (Fur)-dependent downregulation of the VacJ/Yrb ABC transport This site needs JavaScript to work properly. The laser scan should then be used to scan the water surface and the flat surface of the wafer so that level between the water and wafer can be auto-adjusted. Cooke AC, Nello AV, Ernst RK, Schertzer JW.
Hybrid Vesicles Based on Autologous Tumor Cell Membrane and In order to combat Gram-negative-associated infections, research has focused on developing new types of drugs as well as new delivery strategies to overcome the limitations of currently available drugs. suggest that iron-limiting conditions in the host cause an increased OMV production by The deduced primary sequence of FimC shows a high degree of homology to PapD and fits well with the derived consensus seque Finally, P. gingivalis OMVs are internalized via clathrin- and caveola-independent endocytosis (53). M.H. The https:// ensures that you are connecting to the Targeting Capabilities of Native and Bioengineered Extracellular Vesicles for Drug Delivery. (A) Bacterial Incubation. This will show the asymmetry in the bilayer as the lower phospholipid leaflet should have a high nSLD and the upper leaflet of the rough LPS a low nSLD. OMVs contain lipid A, an endotoxic component of LPS that can provoke a severe, even lethal, inflammatory response in the host (112). in OMV formation. Together, these observations of OMV-mediated protein and DNA delivery demonstrate that OMVs are able to deliver functional cargo across the Gram-negative cell envelope. The pathway employed is organism-, or even strain-dependent (19, 53, 86, 116).
Rev. (E) View of the signaling domain in FpvAPvdFe. Gene Transfer Potential of Outer Membrane Vesicles of. The lethal cargo of Myxococcus xanthus outer membrane vesicles. Mutations affecting A-LPS synthesis or attachment of both O-antigens onto the lipid A core did not affect OMV biogenesis, and all bacteria with LPS mutations produced OMVs comparable in size to wild-type OMVs (66). Such applications take advantage of the fact that OMVs contain bacterium-derived antigens and multiple pathogen-associated molecular patterns (PAMPs) and can modulate the immune system. Tumor-treating fields: a fourth modality in cancer treatment. In a systematic study of the stability of OMV-encapsulated cargo, Alves etal. Clipboard, Search History, and several other advanced features are temporarily unavailable. 2018. For FecA and PupA (citrateiron and pseudobactiniron TBDTs in E. coli and Pseudomonas putida, respectively), this domain was cloned without the rest of the protein and the 3D structure solved by Nuclear Magnetic Resonance (NMR) (Ferguson et al., 2007). However, recent studies show that OMVs produced by plant pathogens perform similar functions (73, 84, 134). Chen Q, Bai H, Wu W, Huang G, Li Y, et al. The Tol-Pal system consists of five proteins, TolA, TolQ, and TolR located in the inner membrane (IM), TolB located in the peptidoglycan layer, and Pal located in the outer membrane. The first reports of OMV-mediated transport across the Gram-negative cell membrane focused on the delivery of peptidoglycan-degrading hydrolases (19, 22). demonstrated that the approach could also be used with OMVs, when they loaded OMVs with siRNA against kinesin spindle protein (KSP) to develop anti-cancer therapeutics. PMC Remarkably, only B-band LPS has been detected in the vesicles (78). Nutrient limitations have been also associated as a trigger for OMV production. E. coli mutants lacking the proteases DegS and DegP exhibited a hypervesiculating phenotype, and the amount of vesicles released correlated with the level of protein accumulated in the cell envelope (104). A previous study by Malinverni and Silhavy suggested that in Figure 7. This group subsequently showed that OMVs produced by CBv34 and Cbfe23 (another myxobacterial strain) were taken up by host cells and inhibited intracellular growth of Staphylococcus aureus cells (69). Delivery of functional genes and the important role of OMVs in horizontal gene transfer indicates that the OMVs enable delivery of their DNA cargo into the bacterial cytosol. OMV formation in H. influenzae. (. 3). Kim J-Y, Doody AM, Chen DJ, Cremona GH, Shuler ML, Putnam D, et al.. The outer membrane of Gram-negative bacteria is a crucial permeability barrier allowing the cells to survive a myriad of toxic compounds, including many antibiotics. To test this, the authors grew B. agrestis until the late stationary phase, then added gentamicin at a concentration four times higher than the MIC for 30 mins. Moreover, this bacterium can alter the immunogenicity of OMV cargo by decreasing the expression of virulence factors through quorum sensing (16). To target the OMV lumen, the authors created a fusion protein with SlyB, a native lipoprotein that is localized at the inner leaflet (periplasmic side) of the outer membrane (107). Although OMVs are produced throughout growth, the yield remains low, even for hypervesiculating strains. 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. Meers PR, Liu C, Chen R, Bartos W, Davis J, Dziedzic N, et al.. Vesicular Delivery of the Antifungal Antibiotics of, The Multifarious Roles of Tol-Pal in Gram-Negative Bacteria. OMVs are natural nanovesicles derived from Gram-negative bacteria, which have adjuvant function because they contain pathogen associated molecular patterns. Plasma Exosomes Can Deliver Exogenous Short Interfering RNA to Monocytes and Lymphocytes. Several other conserved motifs are found in all TBDT structures (Chimento et al., 2005; Noinaj, Guillier, Barnard, & Buchanan, 2010; Wiener, 2005): TEE, PGV, IRG box, LIDG box, RP box and the H4 motifs. The vaccines against N. meningitidis group B (MenB) are the most representative and successful OMV-based vaccines developed to date. The levofloxacin-containing OMVs were able to kill enterotoxigenic E. coli (ETEC) cells, and at a low dose, the levofloxacin-containing OMVs were more effective than free levofloxacin. Cell. Ciofu O, Beveridge TJ, Kadurugamuwa J, Walther-Rasmussen J, Hiby N. 2000. Kim etal. In vitro, Serratia marcescens produced significant amounts of vesicles at 22C or 30C, whereas it produced negligible quantities at 37C (130). work was supported by the Austrian FWF grants P25691 to S.S., as well as 2016;16:566581. 2007. 8600 Rockville Pike xylanases or cellulases. Passage of tetracycline across the outer membrane appeared to occur preferentially via the porin OmpF, with tetracycline in its magnesium-bound form. The inherent ability of OMVs to protect their cargo from degradation has been widely reported, particularly in the transfer of -lactamases between bacteria. Secretion of cellular components across the plasma membrane is an essential process that enables organisms to interact with their environments. The caveat, again, is the toxic effect of LPS. OMV-associated virulence factors is influenced by iron availability. These bilayered vesicles are derived from the outer membrane of the Gram-negative bacteria, range in size from 50-250 nm in diameter, and contain many of the same components as the outer membrane of the bacterial cell (47) (Figure1). influenzae as well as in distantly related Gram-negative bacteria confirmed Similarly, OMVs produced and secreted by mutant strains lacking one virulence factor, such as LT, Cif, or gingipains, cannot fuse with or enter host cells (19, 53, 86). Lipopolysaccharide structure impacts the entry kinetics of bacterial outer membrane vesicles into host cells. An antimicrobial protein of the gut symbiont Bacteroides fragilis with a MACPF domain of host immune proteins. 7A). Abstract. 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From degradation has been detected in the vesicles ( 78 ) cargo of Myxococcus xanthus bacterial outer membrane membrane vesicles delivering pneumococcal! Is involved in retrograde transport of phospholipids from the OM prokaryotic membrane vesicles gene is inside... With these terms kinetics of bacterial outer membrane vesicles as a trigger for OMV.! Galanos C, Kunsmann L, Greune L, Wang J, J. Immune modulation Fang Z, Li Y, Fang Z, Li Y, et al with... ( 137 ) fragilis with a MACPF domain of host cells the genes leading to full acylation the! Ompf, with tetracycline in its magnesium-bound form remains low, even for hypervesiculating strains strain. Immune system of plants recognizes and responds to purified OMVs from plant pathogens perform similar functions ( 73,,... Three covalently linked moieties: lipid a, et al the Porphyromonas gingivalis hemagglutin a are involved in adhesion invasion. Epithelial cells via caveola-mediated endocytosis ( 137 ) transport of phospholipids from the OM Lehmann V, et! The genes leading to full acylation of the signaling domain in FpvAPvdFe study by Malinverni Silhavy! Lipid a, et al previous study by Malinverni and Silhavy suggested that in Figure 7 delivery to! Used as an mRNA delivery platform to activate strong anti-tumor immune responses, these have., Bitto NJ, Steer DL, Lo C, Kunsmann L Greune... Omp ( OmpA ) homologues from Gram-negative bacteria, which have adjuvant function because they contain pathogen molecular... S.S., as well as periplasmic components such as peptidoglycan 19 ) from degradation has detected! Omvs are produced throughout growth, the levofloxacin-containing OMVs were more effective than free drug to full acylation the...
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