Bacterial Outer Membrane Vesicles: From Discovery to Applications

Literature Cited

1. 1. 

   Aguilera L, Toloza L, Giménez R, Odena A, Oliveira E et al. 2014. Proteomic analysis of outer membrane vesicles from the probiotic strain Escherichia coli Nissle 1917. Proteomics 14:222–29
   [Google Scholar]
2. 2. 

   Alaniz RC, Deatherage BL, Lara JC, Cookson BT. 2007. Membrane vesicles are immunogenic facsimiles of Salmonella typhimurium that potently activate dendritic cells, prime B and T cell responses, and stimulate protective immunity in vivo. J. Immunol. 179:7692–701
   [Google Scholar]
3. 3. 

   Allan ND, Beveridge TJ. 2003. Gentamicin delivery to Burkholderia cepacia group IIIa strains via membrane vesicles from Pseudomonas aeruginosa PAO1. Antimicrob. Agents Chemother. 47:2962–65
   [Google Scholar]
4. 4. 

   Arigita C, Jiskoot W, Westdijk J, van Ingen C, Hennink WE et al. 2004. Stability of mono- and trivalent meningococcal outer membrane vesicle vaccines. Vaccine 22:629–42
   [Google Scholar]
5. 5. 

   Asensio CJ, Gaillard ME, Moreno G, Bottero D, Zurita E et al. 2011. Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate. Vaccine 29:1649–56
   [Google Scholar]
6. 6. 

   Avci FY, Kasper DL. 2010. How bacterial carbohydrates influence the adaptive immune system. Annu. Rev. Immunol. 28:107–30
   [Google Scholar]
7. 7. 

   Bahar O, Mordukhovich G, Luu DD, Schwessinger B, Daudi A et al. 2016. Bacterial outer membrane vesicles induce plant immune responses. Mol. Plant-Microbe Interact. 29:374–84
   [Google Scholar]
8. 8. 

   Bartolini E, Ianni E, Frigimelica E, Petracca R, Galli G et al. 2013. Recombinant outer membrane vesicles carrying Chlamydia muridarum HtrA induce antibodies that neutralize chlamydial infection in vitro. J. Extracell. Vesicles 2: https://doi.org/10.3402/jev.v2i0.20181
   [Crossref] [Google Scholar]
9. 9. 

   Batista JH, Leal FC, Fukuda TTH, Alcoforado Diniz J, Almeida F et al. 2020. Interplay between two quorum sensing-regulated pathways, violacein biosynthesis and VacJ/Yrb, dictates outer membrane vesicle biogenesis in Chromobacterium violaceum. Environ. Microbiol. 22:2432–42
   [Google Scholar]
10. 10. 

    Bélanger M, Kozarov E, Song H, Whitlock J, Progulske-Fox A. 2012. Both the unique and repeat regions of the Porphyromonas gingivalis hemagglutin A are involved in adhesion and invasion of host cells. Anaerobe 18:128–34
    [Google Scholar]
11. 11. 

    Berleman JE, Allen S, Danielewicz MA, Remis JP, Gorur A et al. 2014. The lethal cargo of Myxococcus xanthus outer membrane vesicles. Front. Microbiol. 5:474
    [Google Scholar]
12. 12. 

    Bernadac A, Gavioli M, Lazzaroni JC, Raina S, Lloubès R 1998. Escherichia coli tol-pal mutants form outer membrane vesicles. J. Bacteriol. 180:4872–78
    [Google Scholar]
13. 13. 

    Bielaszewska M, Marejková M, Bauwens A, Kunsmann-Prokscha L, Mellmann A, Karch H. 2018. Enterohemorrhagic Escherichia coli O157 outer membrane vesicles induce interleukin 8 production in human intestinal epithelial cells by signaling via Toll-like receptors TLR4 and TLR5 and activation of the nuclear factor NF-κB. Int. J. Med. Microbiol. 308:882–89
    [Google Scholar]
14. 14. 

    Bielaszewska M, Rüter C, Bauwens A, Greune L, Jarosch KA et al. 2017. Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: intracellular delivery, trafficking and mechanisms of cell injury. PLOS Pathog 13:e1006159
    [Google Scholar]
15. 15. 

    Bielaszewska M, Rüter C, Kunsmann L, Greune L, Bauwens A et al. 2013. Enterohemorrhagic Escherichia coli hemolysin employs outer membrane vesicles to target mitochondria and cause endothelial and epithelial apoptosis. PLOS Pathog 9:e1003797
    [Google Scholar]
16. 16. 

    Bielig H, Rompikuntal PK, Dongre M, Zurek B, Lindmark B et al. 2011. NOD-like receptor activation by outer membrane vesicles from Vibrio cholerae non-O1 non-O139 strains is modulated by the quorum-sensing regulator HapR. Infect. Immun. 79:1418–27
    [Google Scholar]
17. 17. 

    Bishop DG, Work E. 1965. An extracellular glycolipid produced by Escherichia coli grown under lysine-limiting conditions. Biochem. J. 96:567–76
    [Google Scholar]
18. 18. 

    Blenkiron C, Simonov D, Muthukaruppan A, Tsai P, Dauros P et al. 2016. Uropathogenic Escherichia coli releases extracellular vesicles that are associated with RNA. PLOS ONE 11:e0160440
    [Google Scholar]
19. 19. 

    Bomberger JM, Maceachran DP, Coutermarsh BA, Ye S, O'Toole GA, Stanton BA 2009. Long-distance delivery of bacterial virulence factors by Pseudomonas aeruginosa outer membrane vesicles. PLOS Pathog 5:e1000382
    [Google Scholar]
20. 20. 

    Brameyer S, Plener L, Müller A, Klingl A, Wanner G, Jung K 2018. Outer membrane vesicles facilitate trafficking of the hydrophobic signaling molecule CAI-1 between Vibrio harveyi cells. J. Bacteriol. 200:e00740-17
    [Google Scholar]
21. 21. 

    Brown L, Wolf JM, Prados-Rosales R, Casadevall A. 2015. Through the wall: extracellular vesicles in Gram-positive bacteria, mycobacteria and fungi. Nat. Rev. Microbiol. 13:620–30
    [Google Scholar]
22. 22. 

    Camacho AI, de Souza J, Sánchez-Gómez S, Pardo-Ros M, Irache JM, Gamazo C. 2011. Mucosal immunization with Shigella flexneri outer membrane vesicles induced protection in mice. Vaccine 29:8222–29
    [Google Scholar]
23. 23. 

    Cañas MA, Fábrega MJ, Giménez R, Badia J, Baldomà L. 2018. Outer membrane vesicles from probiotic and commensal Escherichia coli activate NOD1-mediated immune responses in intestinal epithelial cells. Front. Microbiol. 9:498
    [Google Scholar]
24. 24. 

    Carvalho AL, Fonseca S, Miquel-Clopés A, Cross K, Kok KS et al. 2019. Bioengineering commensal bacteria-derived outer membrane vesicles for delivery of biologics to the gastrointestinal and respiratory tract. J. Extracell. Vesicles 8:1632100
    [Google Scholar]
25. 25. 

    Casella CR, Mitchell TC. 2008. Putting endotoxin to work for us: monophosphoryl lipid A as a safe and effective vaccine adjuvant. Cell Mol. Life Sci. 65:3231–40
    [Google Scholar]
26. 26. 

    Celluzzi A, Masotti A. 2016. How our other genome controls our epi-genome. Trends Microbiol 24:777–87
    [Google Scholar]
27. 27. 

    Chatterjee D, Chaudhuri K. 2011. Association of cholera toxin with Vibrio cholerae outer membrane vesicles which are internalized by human intestinal epithelial cells. FEBS Lett 585:1357–62
    [Google Scholar]
28. 28. 

    Chatterjee SN, Das J. 1967. Electron microscopic observations on the excretion of cell-wall material by Vibrio cholerae. J. Gen. Microbiol. 49:1–11
    [Google Scholar]
29. 29. 

    Chatzidaki-Livanis M, Coyne MJ, Comstock LE. 2014. An antimicrobial protein of the gut symbiont Bacteroides fragilis with a MACPF domain of host immune proteins. Mol. Microbiol. 94:1361–74
    [Google Scholar]
30. 30. 

    Chen DJ, Osterrieder N, Metzger SM, Buckles E, Doody AM et al. 2010. Delivery of foreign antigens by engineered outer membrane vesicle vaccines. PNAS 107:3099–104
    [Google Scholar]
31. 31. 

    Chen L, Valentine JL, Huang CJ, Endicott CE, Moeller TD et al. 2016. Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies. PNAS 113:E3609–18
    [Google Scholar]
32. 32. 

    Chen Q, Bai H, Wu W, Huang G, Li Y et al. 2020. Bioengineering bacterial vesicle-coated polymeric nanomedicine for enhanced cancer immunotherapy and metastasis prevention. Nano Lett 20:11–21
    [Google Scholar]
33. 33. 

    Choi DS, Kim DK, Choi SJ, Lee J, Choi JP et al. 2011. Proteomic analysis of outer membrane vesicles derived from Pseudomonas aeruginosa. Proteomics 11:3424–29
    [Google Scholar]
34. 34. 

    Ciofu O, Beveridge TJ, Kadurugamuwa J, Walther-Rasmussen J, Høiby N. 2000. Chromosomal beta-lactamase is packaged into membrane vesicles and secreted from Pseudomonas aeruginosa. J. Antimicrob. Chemother. 45:9–13
    [Google Scholar]
35. 35. 

    Coyne MJ, Béchon N, Matano LM, McEneany VL, Chatzidaki-Livanis M, Comstock LE. 2019. A family of anti-Bacteroidales peptide toxins wide-spread in the human gut microbiota. Nat. Commun. 10:3460
    [Google Scholar]
36. 36. 

    Dauros-Singorenko P, Blenkiron C, Phillips A, Swift S. 2018. The functional RNA cargo of bacterial membrane vesicles. FEMS Microbiol. Lett. 365: https://doi.org/10.1093/femsle/fny023
    [Crossref] [Google Scholar]
37. 37. 

    Davies C, Taylor AJ, Elmi A, Winter J, Liaw J et al. 2019. Sodium taurocholate stimulates Campylobacter jejuni outer membrane vesicle production via down-regulation of the maintenance of lipid asymmetry pathway. Front. Cell Infect. Microbiol. 9:177
    [Google Scholar]
38. 38. 

    Deatherage BL, Cookson BT. 2012. Membrane vesicle release in bacteria, eukaryotes, and archaea: a conserved yet underappreciated aspect of microbial life. Infect. Immun. 80:1948–57
    [Google Scholar]
39. 39. 

    Deatherage BL, Lara JC, Bergsbaken T, Rassoulian Barrett SL, Lara S, Cookson BT 2009. Biogenesis of bacterial membrane vesicles. Mol. Microbiol. 72:1395–407
    [Google Scholar]
40. 40. 

    Delacour D, Greb C, Koch A, Salomonsson E, Leffler H et al. 2007. Apical sorting by galectin-3-dependent glycoprotein clustering. Traffic 8:379–88
    [Google Scholar]
41. 41. 

    DeVoe IW, Gilchrist JE. 1975. Pili on meningococci from primary cultures of nasopharyngeal carriers and cerebrospinal fluid of patients with acute disease. J. Exp. Med. 141:297–305
    [Google Scholar]
42. 42. 

    Duperthuy M, Sjöström AE, Sabharwal D, Damghani F, Uhlin BE, Wai SN. 2013. Role of the Vibrio cholerae matrix protein Bap1 in cross-resistance to antimicrobial peptides. PLOS Pathog 9:e1003620
    [Google Scholar]
43. 43. 

    Elhenawy W, Bording-Jorgensen M, Valguarnera E, Haurat MF, Wine E, Feldman MF. 2016. LPS remodeling triggers formation of outer membrane vesicles in Salmonella. mBio 7:e00940-16
    [Google Scholar]
44. 44. 

    Elhenawy W, Debelyy MO, Feldman MF. 2014. Preferential packing of acidic glycosidases and proteases into Bacteroides outer membrane vesicles. mBio 5:e00909-14
    [Google Scholar]
45. 45. 

    Ellen RP, Grove DA. 1989. Bacteroides gingivalis vesicles bind to and aggregate Actinomyces viscosus. Infect. Immun. 57:1618–20
    [Google Scholar]
46. 46. 

    Ellis TN, Kuehn MJ. 2010. Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbiol. Mol. Biol. Rev. 74:81–94
    [Google Scholar]
47. 47. 

    Ellis TN, Leiman SA, Kuehn MJ. 2010. Naturally produced outer membrane vesicles from Pseudomonas aeruginosa elicit a potent innate immune response via combined sensing of both lipopolysaccharide and protein components. Infect. Immun. 78:3822–31
    [Google Scholar]
48. 48. 

    Elmi A, Dorey A, Watson E, Jagatia H, Inglis NF et al. 2018. The bile salt sodium taurocholate induces Campylobacter jejuni outer membrane vesicle production and increases OMV-associated proteolytic activity. Cell. Microbiol. 20: https://doi.org/10.1111/cmi.12814
    [Crossref] [Google Scholar]
49. 49. 

    Fábrega MJ, Aguilera L, Giménez R, Varela E, Alexandra Cañas M et al. 2016. Activation of immune and defense responses in the intestinal mucosa by outer membrane vesicles of commensal and probiotic Escherichia coli strains. Front. Microbiol. 7:705
    [Google Scholar]
50. 50. 

    Fantappiè L, de Santis M, Chiarot E, Carboni F, Bensi G et al. 2014. Antibody-mediated immunity induced by engineered Escherichia coli OMVs carrying heterologous antigens in their lumen. J. Extracell. Vesicles 3: https://doi.org/10.3402/jev.v3.24015
    [Crossref] [Google Scholar]
51. 51. 

    Florez C, Raab JE, Cooke AC, Schertzer JW. 2017. Membrane distribution of the Pseudomonas quinolone signal modulates outer membrane vesicle production in Pseudomonas aeruginosa. mBio 8:e01034-17
    [Google Scholar]
52. 52. 

    Fransen F, Heckenberg SG, Hamstra HJ, Feller M, Boog CJ et al. 2009. Naturally occurring lipid A mutants in Neisseria meningitidis from patients with invasive meningococcal disease are associated with reduced coagulopathy. PLOS Pathog 5:e1000396
    [Google Scholar]
53. 53. 

    Furuta N, Tsuda K, Omori H, Yoshimori T, Yoshimura F, Amano A. 2009. Porphyromonas gingivalis outer membrane vesicles enter human epithelial cells via an endocytic pathway and are sorted to lysosomal compartments. Infect. Immun. 77:4187–96
    [Google Scholar]
54. 54. 

    Galen JE, Zhao L, Chinchilla M, Wang JY, Pasetti MF et al. 2004. Adaptation of the endogenous Salmonella enterica serovar Typhi clyA-encoded hemolysin for antigen export enhances the immunogenicity of anthrax protective antigen domain 4 expressed by the attenuated live-vector vaccine strain CVD 908-htrA. Infect. Immun. 72:7096–106
    [Google Scholar]
55. 55. 

    Gerding MA, Ogata Y, Pecora ND, Niki H, de Boer PA. 2007. The trans-envelope Tol–Pal complex is part of the cell division machinery and required for proper outer-membrane invagination during cell constriction in E. coli. Mol. Microbiol. 63:1008–25
    [Google Scholar]
56. 56. 

    Gerritzen MJH, Martens DE, Uittenbogaard JP, Wijffels RH, Stork M. 2019. Sulfate depletion triggers overproduction of phospholipids and the release of outer membrane vesicles by Neisseria meningitidis. Sci. Rep. 9:4716
    [Google Scholar]
57. 57. 

    Ghosh A, Saha DR, Hoque KM, Asakuna M, Yamasaki S et al. 2006. Enterotoxigenicity of mature 45-kilodalton and processed 35-kilodalton forms of hemagglutinin protease purified from a cholera toxin gene-negative Vibrio cholerae non-O1, non-O139 strain. Infect. Immun. 74:2937–46
    [Google Scholar]
58. 58. 

    González LJ, Bahr G, Nakashige TG, Nolan EM, Bonomo RA, Vila AJ. 2016. Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase. Nat. Chem. Biol. 12:516–22
    [Google Scholar]
59. 59. 

    González Plaza JJ. 2018. Small RNAs in cell-to-cell communications during bacterial infection. FEMS Microbiol. Lett. 365: https://doi.org/10.1093/femsle/fny024
    [Crossref] [Google Scholar]
60. 60. 

    Grandi A, Fantappiè L, Irene C, Valensin S, Tomasi M et al. 2018. Vaccination with a FAT1-derived B cell epitope combined with tumor-specific B and T cell epitopes elicits additive protection in cancer mouse models. Front. Oncol. 8:481
    [Google Scholar]
61. 61. 

    Grenier D, Bélanger M. 1991. Protective effect of Porphyromonas gingivalis outer membrane vesicles against bactericidal activity of human serum. Infect. Immun. 59:3004–8
    [Google Scholar]
62. 62. 

    Grenier D, Mayrand D. 1987. Functional characterization of extracellular vesicles produced by Bacteroides gingivalis. Infect. Immun. 55:111–17
    [Google Scholar]
63. 63. 

    Guerrero-Mandujano A, Hernández-Cortez C, Ibarra JA, Castro-Escarpulli G. 2017. The outer membrane vesicles: secretion system type zero. Traffic 18:425–32
    [Google Scholar]
64. 64. 

    Guidi R, Levi L, Rouf SF, Puiac S, Rhen M, Frisan T. 2013. Salmonella enterica delivers its genotoxin through outer membrane vesicles secreted from infected cells. Cell Microbiol 15:2034–50
    [Google Scholar]
65. 65. 

    Haurat MF, Aduse-Opoku J, Rangarajan M, Dorobantu L, Gray MR et al. 2011. Selective sorting of cargo proteins into bacterial membrane vesicles. J. Biol. Chem. 286:1269–76
    [Google Scholar]
66. 66. 

    Haurat MF, Elhenawy W, Feldman MF. 2015. Prokaryotic membrane vesicles: new insights on biogenesis and biological roles. Biol. Chem. 396:95–109
    [Google Scholar]
67. 67. 

    Hayashi J, Hamada N, Kuramitsu HK. 2002. The autolysin of Porphyromonas gingivalis is involved in outer membrane vesicle release. FEMS Microbiol. Lett. 216:217–22
    [Google Scholar]
68. 68. 

    Hickey CA, Kuhn KA, Donermeyer DL, Porter NT, Jin C et al. 2015. Colitogenic Bacteroides thetaiotaomicron antigens access host immune cells in a sulfatase-dependent manner via outer membrane vesicles. Cell Host Microbe 17:672–80
    [Google Scholar]
69. 69. 

    Holst J, Oster P, Arnold R, Tatley MV, Næss LM et al. 2013. Vaccines against meningococcal serogroup B disease containing outer membrane vesicles (OMV): lessons from past programs and implications for the future. Hum. Vaccin. Immunother. 9:1241–53
    [Google Scholar]
70. 70. 

    Horspool AM, Schertzer JW. 2018. Reciprocal cross-species induction of outer membrane vesicle biogenesis via secreted factors. Sci. Rep. 8:9873
    [Google Scholar]
71. 71. 

    Horstman AL, Kuehn MJ. 2000. Enterotoxigenic Escherichia coli secretes active heat-labile enterotoxin via outer membrane vesicles. J. Biol. Chem. 275:12489–96
    [Google Scholar]
72. 72. 

    Ionescu M, Zaini PA, Baccari C, Tran S, da Silva AM, Lindow SE. 2014. Xylella fastidiosa outer membrane vesicles modulate plant colonization by blocking attachment to surfaces. PNAS 111:E3910–18
    [Google Scholar]
73. 73. 

    Irene C, Fantappiè L, Caproni E, Zerbini F, Anesi A et al. 2019. Bacterial outer membrane vesicles engineered with lipidated antigens as a platform for Staphylococcus aureus vaccine. PNAS 116:21780–88
    [Google Scholar]
74. 74. 

    Irving AT, Mimuro H, Kufer TA, Lo C, Wheeler R et al. 2014. The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling. Cell Host Microbe 15:623–35
    [Google Scholar]
75. 75. 

    Jäger J, Keese S, Roessle M, Steinert M, Schromm AB. 2015. Fusion of Legionella pneumophila outer membrane vesicles with eukaryotic membrane systems is a mechanism to deliver pathogen factors to host cell membranes. Cell Microbiol 17:607–20
    [Google Scholar]
76. 76. 

    Jones EJ, Booth C, Fonseca S, Parker A, Cross K et al. 2020. The uptake, trafficking, and biodistribution of Bacteroides thetaiotaomicron generated outer membrane vesicles. Front. Microbiol. 11:57
    [Google Scholar]
77. 77. 

    Kadurugamuwa JL, Beveridge TJ. 1995. Virulence factors are released from Pseudomonas aeruginosa in association with membrane vesicles during normal growth and exposure to gentamicin: a novel mechanism of enzyme secretion. J. Bacteriol. 177:3998–4008
    [Google Scholar]
78. 78. 

    Kadurugamuwa JL, Beveridge TJ. 1996. Bacteriolytic effect of membrane vesicles from Pseudomonas aeruginosa on other bacteria including pathogens: conceptually new antibiotics. J. Bacteriol. 178:2767–74
    [Google Scholar]
79. 79. 

    Kamaguchi A, Nakayama K, Ichiyama S, Nakamura R, Watanabe T et al. 2003. Effect of Porphyromonas gingivalis vesicles on coaggregation of Staphylococcus aureus to oral microorganisms. Curr. Microbiol. 47:485–91
    [Google Scholar]
80. 80. 

    Kang CS, Ban M, Choi EJ, Moon HG, Jeon JS et al. 2013. Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis. PLOS ONE 8:e76520
    [Google Scholar]
81. 81. 

    Kaparakis M, Turnbull L, Carneiro L, Firth S, Coleman HA et al. 2010. Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells. Cell Microbiol 12:372–85
    [Google Scholar]
82. 82. 

    Kaparakis-Liaskos M, Ferrero RL. 2015. Immune modulation by bacterial outer membrane vesicles. Nat. Rev. Immunol. 15:375–87
    [Google Scholar]
83. 83. 

    Katsir L, Bahar O. 2017. Bacterial outer membrane vesicles at the plant–pathogen interface. PLOS Pathog 13:e1006306
    [Google Scholar]
84. 84. 

    Kesty NC, Kuehn MJ. 2004. Incorporation of heterologous outer membrane and periplasmic proteins into Escherichia coli outer membrane vesicles. J. Biol. Chem. 279:2069–76
    [Google Scholar]
85. 85. 

    Kesty NC, Mason KM, Reedy M, Miller SE, Kuehn MJ. 2004. Enterotoxigenic Escherichia coli vesicles target toxin delivery into mammalian cells. EMBO J 23:4538–49
    [Google Scholar]
86. 86. 

    Knox KW, Vesk M, Work E. 1966. Relation between excreted lipopolysaccharide complexes and surface structures of a lysine-limited culture of Escherichia coli. J. Bacteriol. 92:1206–17
    [Google Scholar]
87. 87. 

    Kouokam JC, Wai SN, Fällman M, Dobrindt U, Hacker J, Uhlin BE. 2006. Active cytotoxic necrotizing factor 1 associated with outer membrane vesicles from uropathogenic Escherichia coli. Infect. Immun. 74:2022–30
    [Google Scholar]
88. 88. 

    Kovacs-Simon A, Titball RW, Michell SL. 2011. Lipoproteins of bacterial pathogens. Infect. Immun. 79:548–61
    [Google Scholar]
89. 89. 

    Kranz LM, Diken M, Haas H, Kreiter S, Loquai C et al. 2016. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 534:396–401
    [Google Scholar]
90. 90. 

    Kulkarni HM, Nagaraj R, Jagannadham MV. 2015. Protective role of E. coli outer membrane vesicles against antibiotics. Microbiol. Res. 181:1–7
    [Google Scholar]
91. 91. 

    Kunsmann L, Rüter C, Bauwens A, Greune L, Glüder M et al. 2015. Virulence from vesicles: novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain. Sci. Rep. 5:13252
    [Google Scholar]
92. 92. 

    Lappann M, Otto A, Becher D, Vogel U. 2013. Comparative proteome analysis of spontaneous outer membrane vesicles and purified outer membranes of Neisseria meningitidis. J. Bacteriol. 195:4425–35
    [Google Scholar]
93. 93. 

    Lauber F, Cornelis GR, Renzi F. 2016. Identification of a new lipoprotein export signal in Gram-negative bacteria. mBio 7:e01232-16
    [Google Scholar]
94. 94. 

    Li M, Zhou H, Yang C, Wu Y, Zhou X et al. 2020. Bacterial outer membrane vesicles as a platform for biomedical applications: an update. J. Control. Release 323:253–68
    [Google Scholar]
95. 95. 

    Loeb MR. 1974. Bacteriophage T4-mediated release of envelope components from Escherichia coli. J. Virol. 13:631–41
    [Google Scholar]
96. 96. 

    Losier TT, Akuma M, McKee-Muir OC, LeBlond ND, Suk Y et al. 2019. AMPK promotes xenophagy through priming of autophagic kinases upon detection of bacterial outer membrane vesicles. Cell Rep 26:2150–65.e5
    [Google Scholar]
97. 97. 

    Lyczak JB, Cannon CL, Pier GB. 2000. Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect 2:1051–60
    [Google Scholar]
98. 98. 

    Maisonneuve C, Bertholet S, Philpott DJ, De Gregorio E. 2014. Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants. PNAS 111:12294–99
    [Google Scholar]
99. 99. 

    Malinverni JC, Silhavy TJ. 2009. An ABC transport system that maintains lipid asymmetry in the gram-negative outer membrane. PNAS 106:8009–14
    [Google Scholar]
100. 100. 

     Mancini F, Rossi O, Necchi F, Micoli F. 2020. OMV vaccines and the role of TLR agonists in immune response. Int. J. Mol. Sci. 21:4416
     [Google Scholar]
101. 101. 

     Manning AJ, Kuehn MJ. 2011. Contribution of bacterial outer membrane vesicles to innate bacterial defense. BMC Microbiol 11:258
     [Google Scholar]
102. 102. 

     Mashburn LM, Whiteley M. 2005. Membrane vesicles traffic signals and facilitate group activities in a prokaryote. Nature 437:422–25
     [Google Scholar]
103. 103. 

     Mazmanian SK, Round JL, Kasper DL. 2008. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453:620–25
     [Google Scholar]
104. 104. 

     McBroom AJ, Kuehn MJ. 2007. Release of outer membrane vesicles by Gram-negative bacteria is a novel envelope stress response. Mol. Microbiol. 63:545–58
     [Google Scholar]
105. 105. 

     McCaig WD, Loving CL, Hughes HR, Brockmeier SL. 2016. Characterization and vaccine potential of outer membrane vesicles produced by Haemophilus parasuis. PLOS ONE 11:e0149132
     [Google Scholar]
106. 106. 

     Mergenhagen SE, Bladen HA, Hsu KC. 1966. Electron microscopic localization of endotoxic lipopolysaccharide in gram-negative organisms. Ann. N. Y. Acad. Sci. 133:279–91
     [Google Scholar]
107. 107. 

     Micoli F, MacLennan CA. 2020. Outer membrane vesicle vaccines. Semin. Immunol. 50:101433
     [Google Scholar]
108. 108. 

     Molina-Tijeras JA, Gálvez J, Rodríguez-Cabezas ME. 2019. The immunomodulatory properties of extracellular vesicles derived from probiotics: a novel approach for the management of gastrointestinal diseases. Nutrients 11:1038
     [Google Scholar]
109. 109. 

     Mondal A, Tapader R, Chatterjee NS, Ghosh A, Sinha R et al. 2016. Cytotoxic and inflammatory responses induced by outer membrane vesicle-associated biologically active proteases from Vibrio cholerae. Infect. Immun. 84:1478–90
     [Google Scholar]
110. 110. 

     Muralinath M, Kuehn MJ, Roland KL, Curtiss R. 2011. Immunization with Salmonella enterica serovar Typhimurium-derived outer membrane vesicles delivering the pneumococcal protein PspA confers protection against challenge with Streptococcus pneumoniae. Infect. Immun. 79:887–94
     [Google Scholar]
111. 111. 

     Murphy K, Park AJ, Hao Y, Brewer D, Lam JS, Khursigara CM. 2014. Influence of O polysaccharides on biofilm development and outer membrane vesicle biogenesis in Pseudomonas aeruginosa PAO1. J. Bacteriol. 196:1306–17
     [Google Scholar]
112. 112. 

     Nascimento R, Gouran H, Chakraborty S, Gillespie HW, Almeida-Souza HO et al. 2016. The type II secreted lipase/esterase LesA is a key virulence factor required for Xylella fastidiosa pathogenesis in grapevines. Sci. Rep. 6:1–17
     [Google Scholar]
113. 113. 

     Needham BD, Carroll SM, Giles DK, Georgiou G, Whiteley M, Trent MS. 2013. Modulating the innate immune response by combinatorial engineering of endotoxin. PNAS 110:1464–69
     [Google Scholar]
114. 114. 

     Nevermann J, Silva A, Otero C, Oyarzún DP, Barrera B et al. 2019. Identification of genes involved in biogenesis of outer membrane vesicles (OMVs) in Salmonella enterica serovar Typhi. Front. Microbiol. 10:104
     [Google Scholar]
115. 115. 

     Nguyen TT, Saxena A, Beveridge TJ. 2003. Effect of surface lipopolysaccharide on the nature of membrane vesicles liberated from the Gram-negative bacterium Pseudomonas aeruginosa. J. Electron. Microsc. 52:465–69
     [Google Scholar]
116. 116. 

     O'Donoghue EJ, Krachler AM 2016. Mechanisms of outer membrane vesicle entry into host cells. Cell Microbiol 18:1508–17
     [Google Scholar]
117. 117. 

     O'Donoghue EJ, Sirisaengtaksin N, Browning DF, Bielska E, Hadis M et al. 2017. Lipopolysaccharide structure impacts the entry kinetics of bacterial outer membrane vesicles into host cells. PLOS Pathog 13:e1006760
     [Google Scholar]
118. 118. 

     Olivier V, Haines GK, Tan Y, Satchell KJ. 2007. Hemolysin and the multifunctional autoprocessing RTX toxin are virulence factors during intestinal infection of mice with Vibrio cholerae El Tor O1 strains. Infect. Immun. 75:5035–42
     [Google Scholar]
119. 119. 

     Price NL, Goyette-Desjardins G, Nothaft H, Valguarnera E, Szymanski CM et al. 2016. Glycoengineered outer membrane vesicles: a novel platform for bacterial vaccines. Sci. Rep. 6:24931
     [Google Scholar]
120. 120. 

     Rakoff-Nahoum S, Coyne MJ, Comstock LE. 2014. An ecological network of polysaccharide utilization among human intestinal symbionts. Curr. Biol. 24:40–49
     [Google Scholar]
121. 121. 

     Rappazzo CG, Watkins HC, Guarino CM, Chau A, Lopez JL et al. 2016. Recombinant M2e outer membrane vesicle vaccines protect against lethal influenza A challenge in BALB/c mice. Vaccine 34:1252–58
     [Google Scholar]
122. 122. 

     Roier S, Zingl FG, Cakar F, Durakovic S, Kohl P et al. 2016. A novel mechanism for the biogenesis of outer membrane vesicles in Gram-negative bacteria. Nat. Commun. 7:10515
     [Google Scholar]
123. 123. 

     Rompikuntal PK, Thay B, Khan MK, Alanko J, Penttinen AM et al. 2012. Perinuclear localization of internalized outer membrane vesicles carrying active cytolethal distending toxin from Aggregatibacter actinomycetemcomitans. Infect. Immun. 80:31–42
     [Google Scholar]
124. 124. 

     Rompikuntal PK, Vdovikova S, Duperthuy M, Johnson TL, Åhlund M et al. 2015. Outer membrane vesicle-mediated export of processed PrtV protease from Vibrio cholerae. PLOS ONE 10:e0134098
     [Google Scholar]
125. 125. 

     Rothfield L, Pearlman-Kothencz M. 1969. Synthesis and assembly of bacterial membrane components: a lipopolysaccharide-phospholipid-protein complex excreted by living bacteria. J. Mol. Biol. 44:477–92
     [Google Scholar]
126. 126. 

     Round JL, Lee SM, Li J, Tran G, Jabri B et al. 2011. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 332:974–77
     [Google Scholar]
127. 127. 

     Schertzer JW, Whiteley M. 2012. A bilayer-couple model of bacterial outer membrane vesicle biogenesis. mBio 3:e00297-11
     [Google Scholar]
128. 128. 

     Schild S, Nelson EJ, Camilli A. 2008. Immunization with Vibrio cholerae outer membrane vesicles induces protective immunity in mice. Infect. Immun. 76:4554–63
     [Google Scholar]
129. 129. 

     Schwechheimer C, Kuehn MJ. 2013. Synthetic effect between envelope stress and lack of outer membrane vesicle production in Escherichia coli. J. Bacteriol. 195:4161–73
     [Google Scholar]
130. 130. 

     Schwechheimer C, Kuehn MJ. 2015. Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. Nat. Rev. Microbiol. 13:605–19
     [Google Scholar]
131. 131. 

     Shen Y, Giardino Torchia ML, Lawson GW, Karp CL, Ashwell JD, Mazmanian SK 2012. Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe 12:509–20
     [Google Scholar]
132. 132. 

     Sidhu VK, Vorhölter FJ, Niehaus K, Watt SA. 2008. Analysis of outer membrane vesicle associated proteins isolated from the plant pathogenic bacterium Xanthomonas campestris pv. campestris. BMC Microbiol 8:87
     [Google Scholar]
133. 133. 

     Simpson BW, Trent MS. 2019. Pushing the envelope: LPS modifications and their consequences. Nat. Rev. Microbiol. 17:403–16
     [Google Scholar]
134. 134. 

     Sjöström AE, Sandblad L, Uhlin BE, Wai SN. 2015. Membrane vesicle-mediated release of bacterial RNA. Sci. Rep. 5:15329
     [Google Scholar]
135. 135. 

     Solé M, Scheibner F, Hoffmeister A-K, Hartmann N, Hause G et al. 2015.. Xanthomonas campestris pv. vesicatoria secretes proteases and xylanases via the Xps type II secretion system and outer membrane vesicles. J. Bacteriol. 197:2879–93
     [Google Scholar]
136. 136. 

     Song T, Mika F, Lindmark B, Liu Z, Schild S et al. 2008. A new Vibrio cholerae sRNA modulates colonization and affects release of outer membrane vesicles. Mol. Microbiol. 70:100–11
     [Google Scholar]
137. 137. 

     Strauch KL, Johnson K, Beckwith J 1989. Characterization of degP, a gene required for proteolysis in the cell envelope and essential for growth of Escherichia coli at high temperature. J. Bacteriol. 171:2689–96
     [Google Scholar]
138. 138. 

     Turner L, Bitto NJ, Steer DL, Lo C, D'Costa K et al. 2018. Outer membrane vesicle size determines their mechanisms of host cell entry and protein content. Front. Immunol. 9:1466
     [Google Scholar]
139. 139. 

     Valentine JL, Chen L, Perregaux EC, Weyant KB, Rosenthal JA et al. 2016. Immunization with outer membrane vesicles displaying designer glycotopes yields class-switched, glycan-specific antibodies. Cell Chem. Biol. 23:655–65
     [Google Scholar]
140. 140. 

     Valeru SP, Shanan S, Alossimi H, Saeed A, Sandström G, Abd H. 2014. Lack of outer membrane protein A enhances the release of outer membrane vesicles and survival of Vibrio cholerae and suppresses viability of Acanthamoeba castellanii. Int. J. Microbiol. 2014:610190
     [Google Scholar]
141. 141. 

     Valguarnera E, Scott NE, Azimzadeh P, Feldman MF. 2018. Surface exposure and packing of lipoproteins into outer membrane vesicles are coupled processes in Bacteroides. mSphere 3:e00559-18
     [Google Scholar]
142. 142. 

     van der Pol L, Stork M, van der Ley P. 2015. Outer membrane vesicles as platform vaccine technology. Biotechnol. J. 10:1689–706
     [Google Scholar]
143. 143. 

     Veith PD, Chen YY, Gorasia DG, Chen D, Glew MD et al. 2014. Porphyromonas gingivalis outer membrane vesicles exclusively contain outer membrane and periplasmic proteins and carry a cargo enriched with virulence factors. J. Proteome Res. 13:2420–32
     [Google Scholar]
144. 144. 

     Wai SN, Lindmark B, Söderblom T, Takade A, Westermark M et al. 2003. Vesicle-mediated export and assembly of pore-forming oligomers of the enterobacterial ClyA cytotoxin. Cell 115:25–35
     [Google Scholar]
145. 145. 

     Wai SN, Takade A, Amako K. 1995. The release of outer membrane vesicles from the strains of enterotoxigenic Escherichia coli. Microbiol. Immunol. 39:451–56
     [Google Scholar]
146. 146. 

     Wessel AK, Liew J, Kwon T, Marcotte EM, Whiteley M. 2013. Role of Pseudomonas aeruginosa peptidoglycan-associated outer membrane proteins in vesicle formation. J. Bacteriol. 195:213–19
     [Google Scholar]
147. 147. 

     Yeh YC, Comolli LR, Downing KH, Shapiro L, McAdams HH. 2010. The Caulobacter Tol-Pal complex is essential for outer membrane integrity and the positioning of a polar localization factor. J. Bacteriol. 192:4847–58
     [Google Scholar]
148. 148. 

     Zakharzhevskaya NB, Vanyushkina AA, Altukhov IA, Shavarda AL, Butenko IO et al. 2017. Outer membrane vesicles secreted by pathogenic and nonpathogenic Bacteroides fragilis represent different metabolic activities. Sci. Rep. 7:5008
     [Google Scholar]
149. 149. 

     Zhang Y, Fang Z, Li R, Huang X, Liu Q. 2019. Design of outer membrane vesicles as cancer vaccines: a new toolkit for cancer therapy. Cancers 11:1314
     [Google Scholar]
150. 150. 

     Zhou L, Srisatjaluk R, Justus DE, Doyle RJ. 1998. On the origin of membrane vesicles in gram-negative bacteria. FEMS Microbiol. Lett. 163:223–28
     [Google Scholar]