Review Article | Published:

Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions

Nature Reviews Microbiology volume 13, pages 605619 (2015) | Download Citation


Outer-membrane vesicles (OMVs) are spherical buds of the outer membrane filled with periplasmic content and are commonly produced by Gram-negative bacteria. The production of OMVs allows bacteria to interact with their environment, and OMVs have been found to mediate diverse functions, including promoting pathogenesis, enabling bacterial survival during stress conditions and regulating microbial interactions within bacterial communities. Additionally, because of this functional versatility, researchers have begun to explore OMVs as a platform for bioengineering applications. In this Review, we discuss recent advances in the study of OMVs, focusing on new insights into the mechanisms of biogenesis and the functions of these vesicles.

Key points

  • Vesicles derived from the outer membrane of Gram-negative bacteria, or outer-membrane vesicles (OMVs), are heterogeneous in size and composition, encapsulate soluble periplasmic content and are ubiquitously produced. The difficulty in finding a single molecular or genetic basis for OMV production is probably due to species-dependent differences in envelope architecture, environmental influences on envelope composition and redundancy of OMV-producing pathways.

  • Mutations that subtly affect envelope crosslinking affect OMV production, whereas bacterial mutants that are unable to crosslink the envelope are typically unstable and form lysis products instead of OMVs. Lipopolysaccharide (LPS) subtypes also affect the levels of OMV production, as well as OMV cargo recruitment.

  • OMV cargo may be enriched or excluded compared with its abundance in the bacterial envelope, suggesting that cargo recruitment is a regulated rather than stochastic process. Well-characterized cargoes include virulence factors, antibiotic-degrading enzymes, surface adherence factors, proteases and enzymes that are important for nutrient acquisition.

  • OMVs can serve in bacterial communities as 'public goods' by distributing enzymes that break down extracellular material into nutrients, by recruiting iron, by acting as decoys for bacteriophages or antibiotics and by transferring DNA between cells.

  • The versatile characteristics of OMVs and their immunomodulatory properties can be exploited for bioengineering applications and vaccine development.

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This work was supported by US National Institutes of Health grants R01GM099471 and R01AI079068 and by the Duke University Medical Center.

Author information


  1. Department of Biochemistry, Box 3711, Duke University Medical Center, Durham, North Carolina 27710, USA.

    • Carmen Schwechheimer
    •  & Meta J. Kuehn


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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Meta J. Kuehn.


Outer-membrane vesicle

(OMVs). Spherical portions (approximately 20–250 nm in diameter) of the outer membrane of Gram-negative bacteria, containing outer-membrane lipids and proteins, and soluble periplasmic content. OMVs are not the products of cell lysis.


Heterogeneous bacterial communities that are adherent to a surface and often resistant to antibiotics and other chemical disruptants. The attachments between biofilm bacteria and their substrates are typically mediated by extracellular proteins, DNA, polymeric fibres and carbohydrates.


(LPS). A glycolipid found exclusively in the outer leaflet of the outer membrane of Gram-negative bacteria. LPS has a phosphorylated diglucosamine backbone that is typically hexa-acylated and modified with a variable core oligosaccharide and a highly variable O antigen oligosaccharide or polysaccharide chain.

Envelope crosslinks

Covalent and non-covalent links between the peptidoglycan layer and the outer membrane of Gram-negative bacteria.

OMV cargo

(Outer-membrane vesicle cargo). Molecules that are within or associated with outer-membrane vesicles.


The process of producing vesicles. This process may be upregulated (hypervesiculation) or downregulated (hypovesiculation).

Pseudomonas quinolone signal

(PQS). 2-heptyl-3-hydroxy-4-quinolone, an extracellular, hydrophobic quorum sensing signalling molecule that is produced by aerobically grown Pseudomonas aeruginosa. PQS production starts during early stationary phase and is maximal during late stationary phase.

Peptide crosslinks

In the context of this Review: common peptide bonds between the third and fourth residues of two peptide tails in peptidoglycan, catalysed by D,D-transpeptidases and generating D-Ala–meso-diaminopimelic acid crosslinks.

DAP–DAP peptide crosslinks

(Diaminopimelic acid–diaminopimelic acid peptide crosslinks). Fairly uncommon peptide bonds between the third residues of two peptide tails in peptidoglycan, catalysed by L,D-transpeptidases and generating meso-DAP–meso-DAP linkages.

Lytic transglycosylases

Muramidases which cleave the β-(1,4) glycosidic bond between N-acetylmuramic acid and N-acetylglucosamine and participate in cell wall turnover.


Portions of the cell envelope with distinct compositions or biophysical characteristics owing to their specific protein and/or lipid compositions.


Portions of the cell membrane with distinct compositions or biophysical characteristics owing to their specific protein and/or lipid compositions.

Type IV secretion system

A multicomponent protein and DNA translocation complex that traverses the cell envelope and is evolutionarily related to the conjugation system.


Outer-membrane proteins composed of a carboxy-terminal β-barrel translocator domain and an amino-terminal passenger domain that passes through the interior of the barrel to face the external environment.


Surface-associated bacterial molecules that act as ligands or receptors for receptors or ligands on the mammalian host cell, respectively. Typically, adhesins are lectins that bind specific carbohydrate moieties of mammalian glycoproteins and glycolipids.

σE heat shock response

A transcriptional cascade involved in the maintenance, adaptation and protection of the bacterial envelope. The pathway is induced by envelope stress and is mediated by the activation of the σ-factor σE on degradation of the anti-σ-factor in the cytoplasmic membrane, RseA.

SOS response

The coordinated DNA repair pathways that are induced by bacteria in response to DNA damage.


A community of microorganisms that inhabit a particular site.

Bacterial transformation

The stable genetic modification of bacteria with foreign DNA.

Carbapenem resistance

The efflux or enzymatic destruction of carbapenems, a class of broad-spectrum β-lactam antibiotics that inhibit cell wall synthesis.


(S-layer). An outermost envelope layer that commonly occurs in archaea and is also found in bacteria. This layer is composed of a single type of protein or glycoprotein that self-assembles into a crystalline or lattice monomolecular structure.

Haem toxicity

The generation of highly reactive hydroxyl radicals owing to the production of ferrous iron from haem within the reducing environment of cells.


Substances that induce cellular damage through interactions with DNA.

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