Types and origins of bacterial membrane vesicles


Most bacteria release membrane vesicles (MVs) that contain specific cargo molecules and have diverse functions, including the transport of virulence factors, DNA transfer, interception of bacteriophages, antibiotics and eukaryotic host defence factors, cell detoxification and bacterial communication. MVs not only are abundant in nature but also show great promise for applications in biomedicine and nanotechnology. MVs were first discovered to originate from controlled blebbing of the outer membrane of Gram-negative bacteria and are therefore often called outer-membrane vesicles (OMVs). However, recent work has shown that Gram-positive bacteria can produce MVs, that different types of MVs besides OMVs exist and that, in addition to membrane blebbing, MVs can also be formed by endolysin-triggered cell lysis. In this Review, we provide an overview of the structures and compositions of the various vesicle types and discuss novel formation routes, which may lead to distinct vesicle types that serve particular functions.

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Fig. 1: Types of vesicles.
Fig. 2: Different routes lead to the formation of distinct membrane vesicle types.
Fig. 3: Different triggers that induce membrane vesicle formation.
Fig. 4: Roles of membrane vesicles during phage infection.


  1. 1.

    Schwechheimer, C. & Kuehn, M. J. Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. Nat. Rev. Microbiol. 13, 605–619 (2015). This comprehensive Review presents classic models of OMV formation and function.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Brown, L., Wolf, J. M., Prados-Rosales, R. & Casadevall, A. Through the wall: extracellular vesicles in Gram-positive bacteria, mycobacteria and fungi. Nat. Rev. Microbiol. 13, 620–630 (2015). This Review discusses vesicle production by organisms not belonging to the Gram-negative bacteria.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Orench-Rivera, N. & Kuehn, M. J. Environmentally controlled bacterial vesicle-mediated export. Cell. Microbiol. 18, 1525–1536 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Gujrati, V. et al. Bioengineered bacterial outer membrane vesicles as cell-specific drug-delivery vehicles for cancer therapy. ACS Nano 8, 1525–1537 (2014).

    CAS  PubMed  Google Scholar 

  5. 5.

    Kaparakis-Liaskos, M. & Ferrero, R. L. Immune modulation by bacterial outer membrane vesicles. Nat. Rev. Immunol. 15, 375–387 (2015).

    CAS  PubMed  Google Scholar 

  6. 6.

    Biller, S. J. et al. Bacterial vesicles in marine ecosystems. Science 343, 183–186 (2014). This study presents evidence that MVs are abundant in open-ocean samples and demonstrates that the DNA associated with MVs is highly enriched for viral sequences.

    CAS  PubMed  Google Scholar 

  7. 7.

    Grande, R. et al. Helicobacter pylori ATCC 43629/NCTC 11639 outer membrane vesicles (OMVs) from biofilm and planktonic phase associated with extracellular DNA (eDNA). Front. Microbiol. 6, 1369 (2015).

    PubMed  PubMed Central  Google Scholar 

  8. 8.

    Manning, A. J. & Kuehn, M. J. Contribution of bacterial outer membrane vesicles to innate bacterial defense. BMC Microbiol. 11, 258 (2011). This paper demonstrates that OMVs can function as decoys that neutralize phages and membrane-targeting antibiotics.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Toyofuku, M., Roschitzki, B., Riedel, K. & Eberl, L. Identification of proteins associated with the Pseudomonas aeruginosa biofilm extracellular matrix. J. Proteome Res. 11, 4906–4915 (2012).

    CAS  PubMed  Google Scholar 

  10. 10.

    Schooling, S. R. & Beveridge, T. J. Membrane vesicles: an overlooked component of the matrices of biofilms. J. Bacteriol. 188, 5945–5957 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Kulp, A. & Kuehn, M. J. Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu. Rev. Microbiol. 64, 163–184 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Beveridge, T. J. Structures of gram-negative cell walls and their derived membrane vesicles. J. Bacteriol. 181, 4725–4733 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Mashburn-Warren, L. M. & Whiteley, M. Special delivery: vesicle trafficking in prokaryotes. Mol. Microbiol. 61, 839–846 (2006).

    CAS  PubMed  Google Scholar 

  14. 14.

    Turnbull, L. et al. Explosive cell lysis as a mechanism for the biogenesis of bacterial membrane vesicles and biofilms. Nat. Commun. 7, 11220 (2016). This paper demonstrates for the first time that MVs can be formed as a consequence of explosive cell lysis, which is induced by the expression of a phage endolysin.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Toyofuku, M. et al. Prophage-triggered membrane vesicle formation through peptidoglycan damage in Bacillus subtilis. Nat. Commun. 8, 481 (2017). This study shows that CMV production in the Gram-positive bacterium B. subtilis is triggered by the expression of a phage endolysin, a phenomenon named ‘bubbling cell death’.

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Roier, S., Zingl, F. G., Cakar, F. & Schild, S. Bacterial outer membrane vesicle biogenesis: a new mechanism and its implications. Microb. Cell 3, 257–259 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Kulp, A. J. et al. Genome-wide assessment of outer membrane vesicle production in Escherichia coli. PLOS ONE 10, e0139200 (2015).

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Elhenawy, W. et al. LPS remodeling triggers formation of outer membrane vesicles in Salmonella. mBio 7, e00940-16 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Bager, R. J. et al. Outer membrane vesicles reflect environmental cues in Gallibacterium anatis. Vet. Microbiol. 167, 565–572 (2013).

    CAS  PubMed  Google Scholar 

  20. 20.

    Koeppen, K. et al. A novel mechanism of host-pathogen interaction through sRNA in bacterial outer membrane vesicles. PLOS Pathog. 12, e1005672 (2016).

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Sjöström, A. E., Sandblad, L., Uhlin, B. E. & Wai, S. N. Membrane vesicle-mediated release of bacterial RNA. Sci. Rep. 5, 15329 (2015).

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Bitto, N. J. et al. Bacterial membrane vesicles transport their DNA cargo into host cells. Sci. Rep. 7, 7072 (2017).

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Altindis, E., Fu, Y. & Mekalanos, J. J. Proteomic analysis of Vibrio cholerae outer membrane vesicles. Proc. Natl Acad. Sci. USA 111, E1548–E1556 (2014).

    CAS  PubMed  Google Scholar 

  24. 24.

    Wai, S. N. et al. Vesicle-mediated export and assembly of pore-forming oligomers of the enterobacterial ClyA cytotoxin. Cell 115, 25–35 (2003).

    CAS  PubMed  Google Scholar 

  25. 25.

    Guerrero-Mandujano, A., Hernandez-Cortez, C., Ibarra, J. A. & Castro-Escarpulli, G. The outer membrane vesicles: secretion system type zero. Traffic 18, 425–432 (2017).

    CAS  PubMed  Google Scholar 

  26. 26.

    Renelli, M., Matias, V., Lo, R. Y. & Beveridge, T. J. DNA-containing membrane vesicles of Pseudomonas aeruginosa PAO1 and their genetic transformation potential. Microbiology 150, 2161–2169 (2004).

    CAS  PubMed  Google Scholar 

  27. 27.

    Zhou, L., Srisatjaluk, R., Justus, D. E. & Doyle, R. J. On the origin of membrane vesicles in gram-negative bacteria. FEMS Microbiol. Lett. 163, 223–228 (1998).

    CAS  PubMed  Google Scholar 

  28. 28.

    Dorward, D. W. & Garon, C. F. DNA-binding proteins in cells and membrane blebs of Neisseria gonorrhoeae. J. Bacteriol. 171, 4196–4201 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Dorward, D. W. & Garon, C. F. DNA is packaged within membrane-derived vesicles of Gram-negative but not Gram-positive bacteria. Appl. Environ. Microbiol. 56, 1960–1962 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Dorward, D. W., Garon, C. F. & Judd, R. C. Export and intercellular transfer of DNA via membrane blebs of Neisseria gonorrhoeae. J. Bacteriol. 171, 2499–2505 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Kadurugamuwa, J. L. & Beveridge, T. J. 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 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Pérez-Cruz, C. et al. New type of outer membrane vesicle produced by the Gram-negative bacterium Shewanella vesiculosa M7T: implications for DNA content. Appl. Environ. Microbiol. 79, 1874–1881 (2013).

    PubMed  PubMed Central  Google Scholar 

  33. 33.

    Pérez-Cruz, C., Delgado, L., López-Iglesias, C. & Mercade, E. Outer-inner membrane vesicles naturally secreted by gram-negative pathogenic bacteria. PLOS ONE 10, e0116896 (2015).

    PubMed  PubMed Central  Google Scholar 

  34. 34.

    Li, J., Azam, F. & Zhang, S. Outer membrane vesicles containing signalling molecules and active hydrolytic enzymes released by a coral pathogen Vibrio shilonii AK1. Environ. Microbiol. 18, 3850–3866 (2016).

    PubMed  Google Scholar 

  35. 35.

    Hagemann, S. et al. DNA-bearing membrane vesicles produced by Ahrensia kielensis and Pseudoalteromonas marina. J. Basic Microbiol. 54, 1062–1072 (2014).

    CAS  PubMed  Google Scholar 

  36. 36.

    Kadurugamuwa, J. L. & Beveridge, T. J. Natural release of virulence factors in membrane vesicles by Pseudomonas aeruginosa and the effect of aminoglycoside antibiotics on their release. J. Antimicrob. Chemother. 40, 615–621 (1997).

    CAS  PubMed  Google Scholar 

  37. 37.

    Li, Z., Clarke, A. J. & Beveridge, T. J. Gram-negative bacteria produce membrane vesicles which are capable of killing other bacteria. J. Bacteriol. 180, 5478–5483 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Devos, S. et al. Membrane vesicle secretion and prophage induction in multidrug-resistant Stenotrophomonas maltophilia in response to ciprofloxacin stress. Environ. Microbiol. 19, 3930–3937 (2017). This study shows that treatment of S. maltophilia with ciprofloxacin, which is known to induce the SOS response owing to DNA damage, stimulates the production of not only OIMVs but also large amounts of phages.

    CAS  PubMed  Google Scholar 

  39. 39.

    Shingaki, R., Kasahara, Y., Inoue, T., Kokeguchi, S. & Fukui, K. Chromosome DNA fragmentation and excretion caused by defective prophage gene expression in the early-exponential-phase culture of Bacillus subtilis. Can. J. Microbiol. 49, 313–325 (2003).

    CAS  PubMed  Google Scholar 

  40. 40.

    Küsel, K., Dorsch, T., Acker, G. & Stackebrandt, E. Microbial reduction of Fe(III) in acidic sediments: isolation of Acidiphilium cryptum JF-5 capable of coupling the reduction of Fe(III) to the oxidation of glucose. Appl. Environ. Microbiol. 65, 3633–3640 (1999).

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Remis, J. P. et al. Bacterial social networks: structure and composition of Myxococcus xanthus outer membrane vesicle chains. Environ. Microbiol. 16, 598–610 (2014). This study uses several imaging techniques to visualize chains of OMVs in M. xanthus biofilms.

    CAS  PubMed  Google Scholar 

  42. 42.

    Wei, X., Vassallo, C. N., Pathak, D. T. & Wall, D. Myxobacteria produce outer membrane-enclosed tubes in unstructured environments. J. Bacteriol. 196, 1807–1814 (2014).

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    Baidya, A. K., Bhattacharya, S., Dubey, G. P., Mamou, G. & Ben-Yehuda, S. Bacterial nanotubes: a conduit for intercellular molecular trade. Curr. Opin. Microbiol. 42, 1–6 (2017).

    PubMed  Google Scholar 

  44. 44.

    Cao, P., Dey, A., Vassallo, C. N. & Wall, D. How Myxobacteria cooperate. J. Mol. Biol. 427, 3709–3721 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Pirbadian, S. et al. Shewanella oneidensis MR-1 nanowires are outer membrane and periplasmic extensions of the extracellular electron transport components. Proc. Natl Acad. Sci. USA 111, 12883–12888 (2014).

    CAS  PubMed  Google Scholar 

  46. 46.

    Sure, S. K., Ackland, L. M., Torriero, A. A., Adholeya, A. & Kochar, M. Microbial nanowires: an electrifying tale. Microbiology 162, 2017–2028 (2016).

    CAS  PubMed  Google Scholar 

  47. 47.

    McCaig, W. D., Koller, A. & Thanassi, D. G. Production of outer membrane vesicles and outer membrane tubes by Francisella novicida. J. Bacteriol. 195, 1120–1132 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Hampton, C. M. et al. The opportunistic pathogen Vibrio vulnificus produces outer membrane vesicles in a spatially distinct manner related to capsular polysaccharide. Front. Microbiol. 8, 2177 (2017).

    PubMed  PubMed Central  Google Scholar 

  49. 49.

    Dubey, G. P. et al. Architecture and characteristics of bacterial nanotubes. Dev. Cell 36, 453–461 (2016).

    CAS  PubMed  Google Scholar 

  50. 50.

    Dubey, G. P. & Ben-Yehuda, S. Intercellular nanotubes mediate bacterial communication. Cell 144, 590–600 (2011).

    CAS  PubMed  Google Scholar 

  51. 51.

    Sutterlin, H. A. et al. Disruption of lipid homeostasis in the Gram-negative cell envelope activates a novel cell death pathway. Proc. Natl Acad. Sci. USA 113, E1565–E1574 (2016).

    CAS  PubMed  Google Scholar 

  52. 52.

    Hoekstra, D., van der Laan, J. W., de Leij, L. & Witholt, B. Release of outer membrane fragments from normally growing Escherichia coli. Biochim. Biophys. Acta 455, 889–899 (1976).

    CAS  PubMed  Google Scholar 

  53. 53.

    Burdett, I. D. & Murray, R. G. Electron microscope study of septum formation in Escherichia coli strains B and B/r during synchronous growth. J. Bacteriol. 119, 1039–1056 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Deatherage, B. L. et al. Biogenesis of bacterial membrane vesicles. Mol. Microbiol. 72, 1395–1407 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Bernadac, A., Gavioli, M., Lazzaroni, J. C., Raina, S. & Lloubés, R. Escherichia coli tol-pal mutants form outer membrane vesicles. J. Bacteriol. 180, 4872–4878 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Sonntag, I., Schwarz, H., Hirota, Y. & Henning, U. Cell envelope and shape of Escherichia coli: multiple mutants missing the outer membrane lipoprotein and other major outer membrane proteins. J. Bacteriol. 136, 280–285 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Yem, D. W. & Wu, H. C. Physiological characterization of an Escherichia coli mutant altered in the structure of murein lipoprotein. J. Bacteriol. 133, 1419–1426 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Murata, M., Noor, R., Nagamitsu, H., Tanaka, S. & Yamada, M. Novel pathway directed by sigma E to cause cell lysis in Escherichia coli. Genes Cells 17, 234–247 (2012).

    CAS  PubMed  Google Scholar 

  59. 59.

    McBroom, A. J., Johnson, A. P., Vemulapalli, S. & Kuehn, M. J. Outer membrane vesicle production by Escherichia coli is independent of membrane instability. J. Bacteriol. 188, 5385–5392 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Schwechheimer, C., Rodriguez, D. L. & Kuehn, M. J. NlpI-mediated modulation of outer membrane vesicle production through peptidoglycan dynamics in Escherichia coli. MicrobiologyOpen 4, 375–389 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Roier, S. et al. A novel mechanism for the biogenesis of outer membrane vesicles in Gram-negative bacteria. Nat. Commun. 7, 10515 (2016). This study demonstrates that iron limitation controls OMV formation by affecting expression of phospholipid transporter genes in H. influenzae.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    McBroom, A. J. & Kuehn, M. J. Release of outer membrane vesicles by Gram-negative bacteria is a novel envelope stress response. Mol. Microbiol. 63, 545–558 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Tashiro, Y. et al. Outer membrane machinery and alginate synthesis regulators control membrane vesicle production in Pseudomonas aeruginosa. J. Bacteriol. 191, 7509–7519 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Florez, C., Raab, J. E., Cooke, A. C. & Schertzer, J. W. Membrane distribution of the Pseudomonas quinolone signal modulates outer membrane vesicle production in Pseudomonas aeruginosa. mBio 8, e01034-17 (2017).

    PubMed  PubMed Central  Google Scholar 

  65. 65.

    Mashburn, L. M. & Whiteley, M. Membrane vesicles traffic signals and facilitate group activities in a prokaryote. Nature 437, 422–425 (2005).

    CAS  PubMed  Google Scholar 

  66. 66.

    Schertzer, J. W. & Whiteley, M. A bilayer-couple model of bacterial outer membrane vesicle biogenesis. mBio 3, e00297-11 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Mashburn-Warren, L. et al. Interaction of quorum signals with outer membrane lipids: insights into prokaryotic membrane vesicle formation. Mol. Microbiol. 69, 491–502 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Kadurugamuwa, J. L. & Beveridge, T. J. Bacteriolytic effect of membrane vesicles from Pseudomonas aeruginosa on other bacteria including pathogens: conceptually new antibiotics. J. Bacteriol. 178, 2767–2774 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Fulsundar, S. et al. Gene transfer potential of outer membrane vesicles of Acinetobacter baylyi and effects of stress on vesiculation. Appl. Environ. Microbiol. 80, 3469–3483 (2014).

    PubMed  PubMed Central  Google Scholar 

  70. 70.

    Brennan, C. A. et al. A model symbiosis reveals a role for sheathed-flagellum rotation in the release of immunogenic lipopolysaccharide. eLife 3, e01579 (2014).

    PubMed  PubMed Central  Google Scholar 

  71. 71.

    Aschtgen, M. S. et al. Rotation of Vibrio fischeri flagella produces outer membrane vesicles that induce host development. J. Bacteriol. 198, 2156–2165 (2016). This study identifies a unique mechanism of OMV formation that is based on the rotation of membrane-sheathed flagella.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Aschtgen, M. S., Wetzel, K., Goldman, W., McFall-Ngai, M. & Ruby, E. Vibrio fischeri-derived outer membrane vesicles trigger host development. Cell. Microbiol. 18, 488–499 (2016).

    CAS  PubMed  Google Scholar 

  73. 73.

    Geis, G., Suerbaum, S., Forsthoff, B., Leying, H. & Opferkuch, W. Ultrastructure and biochemical studies of the flagellar sheath of Helicobacter pylori. J. Med. Microbiol. 38, 371–377 (1993).

    CAS  PubMed  Google Scholar 

  74. 74.

    Qin, Z., Lin, W. T., Zhu, S., Franco, A. T. & Liu, J. Imaging the motility and chemotaxis machineries in Helicobacter pylori by cryo-electron tomography. J. Bacteriol. 199, e00695–16 (2016).

    PubMed  Google Scholar 

  75. 75.

    Toyofuku, M. et al. Membrane vesicle formation is associated with pyocin production under denitrifying conditions in Pseudomonas aeruginosa PAO1. Environ. Microbiol. 16, 2927–2938 (2014).

    CAS  PubMed  Google Scholar 

  76. 76.

    Wang, X., Thompson, C. D., Weidenmaier, C. & Lee, J. C. Release of Staphylococcus aureus extracellular vesicles and their application as a vaccine platform. Nat. Commun. 9, 1379 (2018).

    PubMed  PubMed Central  Google Scholar 

  77. 77.

    Hayashi, J., Hamada, N. & Kuramitsu, H. K. The autolysin of Porphyromonas gingivalis is involved in outer membrane vesicle release. FEMS Microbiol. Lett. 216, 217–222 (2002).

    CAS  PubMed  Google Scholar 

  78. 78.

    Koning, R. I. et al. Cryo-electron tomography analysis of membrane vesicles from Acinetobacter baumannii ATCC19606 T. Res. Microbiol. 164, 397–405 (2013).

    CAS  PubMed  Google Scholar 

  79. 79.

    Shetty, A. & Hickey, W. J. Effects of outer membrane vesicle formation, surface-layer production and nanopod development on the metabolism of phenanthrene by Delftia acidovorans Cs1-4. PLOS ONE 9, e92143 (2014).

    PubMed  PubMed Central  Google Scholar 

  80. 80.

    Borneleit, P., Hermsdorf, T., Claus, R., Walther, P. & Kleber, H. P. Effect of hexadecane-induced vesiculation on the outer membrane of Acinetobacter calcoaceticus. J. Gen. Microbiol. 134, 1983–1992 (1988).

    CAS  PubMed  Google Scholar 

  81. 81.

    Kobayashi, H., Uematsu, K., Hirayama, H. & Horikoshi, K. Novel toluene elimination system in a toluene-tolerant microorganism. J. Bacteriol. 182, 6451–6455 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Feiner, R. et al. A new perspective on lysogeny: prophages as active regulatory switches of bacteria. Nat. Rev. Microbiol. 13, 641–650 (2015).

    CAS  PubMed  Google Scholar 

  83. 83.

    Catalão, M. J., Gil, F., Moniz-Pereira, J., São-José, C. & Pimentel, M. Diversity in bacterial lysis systems: bacteriophages show the way. FEMS Microbiol. Rev. 37, 554–571 (2013).

    PubMed  Google Scholar 

  84. 84.

    Pennington, J. M. & Rosenberg, S. M. Spontaneous DNA breakage in single living Escherichia coli cells. Nat. Genet. 39, 797–802 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Taddei, F., Matic, I. & Radman, M. cAMP-dependent SOS induction and mutagenesis in resting bacterial populations. Proc. Natl Acad. Sci. USA 92, 11736–11740 (1995).

    CAS  PubMed  Google Scholar 

  86. 86.

    Bernier, S. P. et al. Starvation, together with the SOS response, mediates high biofilm-specific tolerance to the fluoroquinolone ofloxacin. PLOS Genet. 9, e1003144 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Okshevsky, M. & Meyer, R. L. The role of extracellular DNA in the establishment, maintenance and perpetuation of bacterial biofilms. Crit. Rev. Microbiol. 41, 341–352 (2015).

    CAS  PubMed  Google Scholar 

  88. 88.

    Scholl, D. Phage tail-like bacteriocins. Annu. Rev. Virol. 4, 453–467 (2017).

    CAS  PubMed  Google Scholar 

  89. 89.

    Domingues, S. & Nielsen, K. M. Membrane vesicles and horizontal gene transfer in prokaryotes. Curr. Opin. Microbiol. 38, 16–21 (2017).

    CAS  PubMed  Google Scholar 

  90. 90.

    Ho, M. H., Chen, C. H., Goodwin, J. S., Wang, B. Y. & Xie, H. Functional advantages of Porphyromonas gingivalis vesicles. PLOS ONE 10, e0123448 (2015).

    PubMed  PubMed Central  Google Scholar 

  91. 91.

    Kolling, G. L. & Matthews, K. R. Export of virulence genes and Shiga toxin by membrane vesicles of Escherichia coli O157:H7. Appl. Environ. Microbiol. 65, 1843–1848 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Yaron, S., Kolling, G. L., Simon, L. & Matthews, K. R. Vesicle-mediated transfer of virulence genes from Escherichia coli O157:H7 to other enteric bacteria. Appl. Environ. Microbiol. 66, 4414–4420 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Rumbo, C. et al. Horizontal transfer of the OXA-24 carbapenemase gene via outer membrane vesicles: a new mechanism of dissemination of carbapenem resistance genes in Acinetobacter baumannii. Antimicrob. Agents Chemother. 55, 3084–3090 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94.

    Blesa, A. & Berenguer, J. Contribution of vesicle-protected extracellular DNA to horizontal gene transfer in Thermus spp. Int. Microbiol. 18, 177–187 (2015).

    CAS  PubMed  Google Scholar 

  95. 95.

    Klieve, A. V. et al. Naturally occurring DNA transfer system associated with membrane vesicles in cellulolytic Ruminococcus spp. of ruminal origin. Appl. Environ. Microbiol. 71, 4248–4253 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. 96.

    Tashiro, Y. et al. Interaction of bacterial membrane vesicles with specific species and their potential for delivery to target cells. Front. Microbiol. 8, 571 (2017).

    PubMed  PubMed Central  Google Scholar 

  97. 97.

    Li, Z., Clarke, A. J. & Beveridge, T. J. A major autolysin of Pseudomonas aeruginosa: subcellular distribution, potential role in cell growth and division and secretion in surface membrane vesicles. J. Bacteriol. 178, 2479–2488 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. 98.

    Prangishvili, D. et al. Sulfolobicins, specific proteinaceous toxins produced by strains of the extremely thermophilic archaeal genus Sulfolobus. J. Bacteriol. 182, 2985–2988 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. 99.

    Seccareccia, I., Kost, C. & Nett, M. Quantitative analysis of Lysobacter predation. Appl. Environ. Microbiol. 81, 7098–7105 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. 100.

    Casida, L. E. Minireview: Nonobligate bacterial predation of bacteria in soil. Microb. Ecol. 15, 1–8 (1988).

    PubMed  Google Scholar 

  101. 101.

    Vasilyeva, N. V., Tsfasman, I. M., Suzina, N. E., Stepnaya, O. A. & Kulaev, I. S. Secretion of bacteriolytic endopeptidase L5 of Lysobacter sp. XL1 into the medium by means of outer membrane vesicles. FEBS J. 275, 3827–3835 (2008).

    CAS  PubMed  Google Scholar 

  102. 102.

    Kudryakova, I. V., Suzina, N. E., Vinokurova, N. G., Shishkova, N. A. & Vasilyeva, N. V. Studying factors involved in biogenesis of Lysobacter sp. XL1 outer membrane vesicles. Biochemistry (Mosc.) 82, 501–509 (2017).

    CAS  Google Scholar 

  103. 103.

    Kudryakova, I. V., Suzina, N. E. & Vasilyeva, N. V. Biogenesis of Lysobacter sp. XL1 vesicles. FEMS Microbiol. Lett. 362, fnv137 (2015).

    PubMed  Google Scholar 

  104. 104.

    Tzipilevich, E., Habusha, M. & Ben-Yehuda, S. Acquisition of phage sensitivity by bacteria through exchange of phage receptors. Cell 168, 186–199 (2017). The study demonstrates that CMVs can transmit phage receptors to phage-resistant cells, which then become phage sensitive.

    CAS  PubMed  Google Scholar 

  105. 105.

    Kharina, A. et al. Temperate bacteriophages collected by outer membrane vesicles in Komagataeibacter intermedius. J. Basic Microbiol. 55, 509–513 (2015).

    CAS  Google Scholar 

  106. 106.

    Manning, A. J. & Kuehn, M. J. Functional advantages conferred by extracellular prokaryotic membrane vesicles. J. Mol. Microbiol. Biotechnol. 23, 131–141 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Reyes-Robles, T. et al. Vibrio cholerae outer membrane vesicles inhibit bacteriophage infection. J. Bacteriol. https://doi.org/10.1128/JB.00792-17 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  108. 108.

    Toyofuku, M. et al. Membrane vesicle-mediated bacterial communication. ISME J. 11, 1504–1509 (2017).

    PubMed  PubMed Central  Google Scholar 

  109. 109.

    Devos, S. et al. The effect of imipenem and diffusible signaling factors on the secretion of outer membrane vesicles and associated Ax21 proteins in Stenotrophomonas maltophilia. Front. Microbiol. 6, 298 (2015).

    PubMed  PubMed Central  Google Scholar 

  110. 110.

    Ionescu, M. et al. Xylella fastidiosa outer membrane vesicles modulate plant colonization by blocking attachment to surfaces. Proc. Natl Acad. Sci. USA 111, E3910–E3918 (2014).

    CAS  PubMed  Google Scholar 

  111. 111.

    Lynch, J. B. & Alegado, R. A. Spheres of hope, packets of doom: the good and bad of outer membrane vesicles in interspecies and ecological dynamics. J. Bacteriol. 199, e00012-17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. 112.

    Aung, K. M. et al. Naturally occurring IgG antibodies provide innate protection against Vibrio cholerae bacteremia by recognition of the outer membrane protein U. J. Innate Immun. 8, 269–283 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. 113.

    Duperthuy, M. et al. Role of the Vibrio cholerae matrix protein Bap1 in cross-resistance to antimicrobial peptides. PLOS Pathog. 9, e1003620 (2013).

    PubMed  PubMed Central  Google Scholar 

  114. 114.

    Codemo, M. et al. Immunomodulatory effects of pneumococcal extracellular vesicles on cellular and humoral host defenses. mBio 9, e00559-18 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. 115.

    Kimmitt, P. T., Harwood, C. R. & Barer, M. R. Toxin gene expression by shiga toxin-producing Escherichia coli: the role of antibiotics and the bacterial SOS response. Emerg. Infect. Dis. 6, 458–465 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. 116.

    Quinones, M., Kimsey, H. H. & Waldor, M. K. LexA cleavage is required for CTX prophage induction. Mol. Cell 17, 291–300 (2005).

    CAS  PubMed  Google Scholar 

  117. 117.

    Chatterjee, D. & Chaudhuri, K. Association of cholera toxin with Vibrio cholerae outer membrane vesicles which are internalized by human intestinal epithelial cells. FEBS Lett. 585, 1357–1362 (2011).

    CAS  PubMed  Google Scholar 

  118. 118.

    Bielaszewska, M. et al. 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 (2017).

    PubMed  PubMed Central  Google Scholar 

  119. 119.

    Kunsmann, L. et al. Virulence from vesicles: Novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain. Sci. Rep. 5, 13252 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120.

    Gaudin, M. et al. Extracellular membrane vesicles harbouring viral genomes. Environ. Microbiol. 16, 1167–1175 (2014). This study shows that MVs can harbour viral genomes, suggesting a link between phage release and vesicle formation.

    CAS  PubMed  Google Scholar 

  121. 121.

    Biller, S. J. et al. Membrane vesicles in sea water: heterogeneous DNA content and implications for viral abundance estimates. ISME J. 11, 394–404 (2017).

    CAS  PubMed  Google Scholar 

  122. 122.

    Soler, N., Krupovic, M., Marguet, E. & Forterre, P. Membrane vesicles in natural environments: a major challenge in viral ecology. ISME J. 9, 793–796 (2015).

    CAS  PubMed  Google Scholar 

  123. 123.

    Gamalier, J. P., Silva, T. P., Zarantonello, V., Dias, F. F. & Melo, R. C. Increased production of outer membrane vesicles by cultured freshwater bacteria in response to ultraviolet radiation. Microbiol. Res. 194, 38–46 (2017).

    CAS  PubMed  Google Scholar 

  124. 124.

    Breitbart, M. & Rohwer, F. Here a virus, there a virus, everywhere the same virus? Trends Microbiol. 13, 278–284 (2005).

    CAS  PubMed  Google Scholar 

  125. 125.

    Radman, M. SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis. Basic Life Sci. 5A, 355–367 (1975).

    CAS  PubMed  Google Scholar 

  126. 126.

    Kenyon, C. J. & Walker, G. C. DNA-damaging agents stimulate gene-expression at specific loci in Escherichia coli. Proc. Natl Acad. Sci. USA 77, 2819–2823 (1980).

    CAS  PubMed  Google Scholar 

  127. 127.

    Fernandez De Henestrosa, A. R. et al. Identification of additional genes belonging to the LexA regulon in Escherichia coli. Mol. Microbiol. 35, 1560–1572 (2000).

    CAS  PubMed  Google Scholar 

  128. 128.

    McPartland, A., Green, L. & Echols, H. Control of recA gene RNA in E. coli: regulatory and signal genes. Cell 20, 731–737 (1980).

    CAS  PubMed  Google Scholar 

  129. 129.

    Little, J. W., Edmiston, S. H., Pacelli, L. Z. & Mount, D. W. Cleavage of the Escherichia coli LexA protein by the RecA protease. Proc. Natl Acad. Sci. USA 77, 3225–3229 (1980).

    CAS  PubMed  Google Scholar 

  130. 130.

    Michel, B. After 30 years of study, the bacterial SOS response still surprises us. PLOS Biol. 3, e255 (2005).

    PubMed  PubMed Central  Google Scholar 

  131. 131.

    Tippin, B., Pham, P. & Goodman, M. F. Error-prone replication for better or worse. Trends Microbiol. 12, 288–295 (2004).

    CAS  PubMed  Google Scholar 

  132. 132.

    Fuchs, R. P. & Fujii, S. Translesion DNA synthesis and mutagenesis in prokaryotes. Cold Spring Harb. Perspect. Biol. 5, a012682 (2013).

    PubMed  PubMed Central  Google Scholar 

  133. 133.

    Schoemaker, J. M., Gayda, R. C. & Markovitz, A. Regulation of cell division in Escherichia coli: SOS induction and cellular location of the SulA protein, a key to lon-associated filamentation and death. J. Bacteriol. 158, 551–561 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. 134.

    Little, J. W. & Harper, J. E. Identification of the lexA gene product of Escherichia coli K-12. Proc. Natl Acad. Sci. USA 76, 6147–6151 (1979).

    CAS  PubMed  Google Scholar 

  135. 135.

    Craig, N. L. & Roberts, J. W. E. coli RecA protein-directed cleavage of phage lambda repressor requires polynucleotide. Nature 283, 26–30 (1980).

    CAS  PubMed  Google Scholar 

  136. 136.

    Biagini, M. et al. The human pathogen Streptococcus pyogenes releases lipoproteins as lipoprotein-rich membrane vesicles. Mol. Cell. Proteomics 14, 2138–2149 (2015).

    CAS  Google Scholar 

  137. 137.

    Wichgers Schreur, P. J., Rebel, J. M., Smits, M. A., van Putten, J. P. & Smith, H. E. Lgt processing is an essential step in Streptococcus suis lipoprotein mediated innate immune activation. PLOS ONE 6, e22299 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. 138.

    Maredia, R. et al. Vesiculation from Pseudomonas aeruginosa under SOS. Sci. World J. 2012, 402919 (2012).

    Google Scholar 

  139. 139.

    Bauwens, A., Kunsmann, L., Karch, H., Mellmann, A. & Bielaszewska, M. Antibiotic-mediated modulations of outer membrane vesicles in enterohemorrhagic Escherichia coli O104:H4 and O157:H7. Antimicrob. Agents Chemother. 61, e00937-17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. 140.

    Kadurugamuwa, J. L., Clarke, A. J. & Beveridge, T. J. Surface action of gentamicin on Pseudomonas aeruginosa. J. Bacteriol. 175, 5798–5805 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. 141.

    Hoefler, B. C. et al. A link between linearmycin biosynthesis and extracellular vesicle genesis connects specialized metabolism and bacterial membrane physiology. Cell Chem. Biol. 24, 1238–1249.e7 (2017).

    CAS  PubMed  Google Scholar 

  142. 142.

    Freedman, S. B. et al. Shiga toxin–producing Escherichia coli infection, antibiotics, and risk of developing hemolytic uremic syndrome: a meta-analysis. Clin. Infect. Dis. 62, 1251–1258 (2016).

    PubMed  PubMed Central  Google Scholar 

  143. 143.

    MacDonald, K. L. & Beveridge, T. J. Bactericidal effect of gentamicin-induced membrane vesicles derived from Pseudomonas aeruginosa PAO1 on Gram-positive bacteria. Can. J. Microbiol. 48, 810–820 (2002).

    CAS  PubMed  Google Scholar 

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M.T. was supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) (project 16H06189), N.N. was supported by the Japan Science and Technology Agency (JST) (ERATO project JPMJER1502), and L.E. was supported by the Swiss National Science Foundation (SNSF) (Project 31003A_169307). The authors acknowledge K. Agnoli-Antkowiak for valuable comments on the manuscript.

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Nature Reviews Microbiology thanks S. Schild, S. N. Wai and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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M.T. and L.E. researched data for the article and contributed substantially to discussion of the content. All authors wrote the article and reviewed and edited the manuscript before submission.

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Correspondence to Masanori Toyofuku or Leo Eberl.

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Hydrolytic enzymes that are produced by bacteriophages to degrade the cell wall of the bacterial host during the final stage of the lytic cycle.


Peptidoglycan hydrolases that are produced by bacteria for peptidoglycan turnover and to complete cell division by separating the daughter cell from the mother cell.


The reversible insertion of molecules into materials with layered structures such as the cellular membrane.

Turgor pressure

Turgor is the force that pushes the cytoplasmic membrane against the cell wall as a result of the osmotic flow of water.

Quorum sensing

A cell-to-cell communication mechanism in bacteria by which gene regulation is controlled in a population-dependent manner through the production and perception of signal molecules.

B-band LPS

Pseudomonas aeruginosa synthesizes two types of lipopolysaccharide (LPS) referred to as A-band and B-band LPS. The A-band LPS contains a conserved O-polysaccharide region composed of d-rhamnose (homopolymer), whereas the B-band O-antigen (heteropolymer) structure varies among different serotypes.


Protein or peptide toxins produced by bacteria to kill or inhibit growth of bacteria that are closely related to the producer.

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Toyofuku, M., Nomura, N. & Eberl, L. Types and origins of bacterial membrane vesicles. Nat Rev Microbiol 17, 13–24 (2019). https://doi.org/10.1038/s41579-018-0112-2

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