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Bacterial outer membrane vesicles

File:Human Salmonella secreting outer membrane vesicles in vivo in chicken ileum (Original work of Dr R C YashRoy).png
Fig. 1 Transmission electron micrograph of outer membrane vesicles (OMV) (size 80-90 nm, dia) released by human pathogen Salmonella 3,10:r:- in chicken ileum, in vivo. OMVs were proposed to be 'blown off' from large bacterial periplasmic protrusions, called periplasmic organelles (PO) with the help of 'bubble tube'-like assembly of about four type III secretion injectisomal rivet complexes (riveting bacterial outer and cell membrane to allow pockets of periplasm to expand into POs). This allows membrane vesicle trafficking of OMVs from gram negative bacteria to dock on host epithelial cell membrane (microvilli), proposed to translocate signal molecules from pathogen to host cells at the host-pathogen interface.

Bacteria communicate among themselves and with other living forms in their environment via nano-scale membrane vesicles in their bacterial outer membranes. These vesicles are involved in trafficking bacterial cell signaling biochemicals, which may include DNA, RNA, proteins, endotoxins and allied virulence molecules. This communication happens in microbial cultures to oceans,[1] inside animal/plant hosts and wherever bacteria may thrive. Gram negative microorganisms deploy their periplasm to secrete bacterial outer membrane vesicles (OMVs) for trafficking bacterial biochemicals to target cells in their environment (Fig. 1); OMVs also carry endotoxic lipopolysaccharide initiating disease process in their host.[2] This mechanism imparts a variety of benefits like, long-distance delivery of bacterial secretory cargo with minimized hydrolytic degradation and extra-cellular dilution, also supplemented with other supportive molecules (e.g., virulence factors) to accomplish a specific job and yet, keeping a safe-distance from the defense arsenal of the targeted cells. Biochemical signals trafficked by OMVs may vary largely during 'war and peace' situations. In 'complacent' bacterial colonies, OMVs may be used to carry DNA to 'related' microbes for genetic transformations, and also translocate cell signaling molecules for quorum sensing and biofilm formation. During 'challenge' from other cell types around, OMVs may be preferred to carry degradation and subversion enzymes. Likewise, OMVs may contain more of invasion proteins at the host-pathogen interface (Fig. 1). It is expected, that environmental factors around the secretory microbes are responsible for inducing these bacteria to synthesize and secrete specifically-enriched OMVs, physiologically suiting the immediate task. Thus, bacterial OMVs, being strong immunomodulators,[3] can be manipulated for their immunogenic contents and utilized as potent pathogen-free vaccines[4] for immunizing humans and animals against threatening infections.

Biogenesis of bacterial OMVs

Gram negative microbes have a double set of covering membranes. A cell membrane encloses the bacterial cytoplasm or cytosol, and over the cell membrane, there is another membrane called bacterial outer membrane. The compartment or space between these two membranes is called periplasm or periplasmic space. In addition, there is a firm cell wall consisting of peptidoglycan layer, which surrounds the cell membrane. Peptidoglycan layer provides some rigidity for maintaining the bacterial cell shape, besides also protecting the microbe against challenging environment. Thus, periplasm ensures expandable and additional space for storing microbial cell secretions, for further and strategic use via a specialized secretory pathway. Size and contents of periplasm are therefore, variable as per physiological requirements (Fig. 2).
Fig. 2 Transmission electron micrograph of a bulge of Salmonella organism in animal host tissue. Space bar: 100nm, Line-arrow, O: outer membrane, P: periplasm, bold arrow: peptidoglycan layer

The first step in biogenesis of gram negative bacterial OMVs,[5] is bulging of outer membrane above the peptidoglycan layer (Fig 2). It has been suggested (links) that few supramolecular proteins may 'rivet' the outer and cell membranes together, so that the periplasmic bulge protrudes like a 'ballooned' pocket of inflated periplasm. Lateral diffusion of 'rivet complexes' may help in pinching off large bulges of periplasm as OMVs.[6] Detailed experimental work is still awaited to understand the biomechanics of OMV biogenesis. OMVs are also under focus of current research in exocytosis in prokaryotes via outer membrane vesicle trafficking for intra-species, inter-species and inter-kingdom cell signaling, which is slated to change our mindset on virulence of microbes, host-pathogen interactions and inter-relationships among variety of species in earth's ecosystem.

See also


  1. ^ Biller JJ, Schubotz F, Thompson AW, Summons RE and Chisholm SW (2014) Bacterial vesicles in marine ecosystems. Science, vol. 343(no. 6167), pp. 183-186.
  2. ^ YashRoy R C (1993) Electron microscope studies of surface pili and vesicles of Salmonella 3,10:r:- organisms. Indian Journal of Animal Sciences, vol. 63 (No.2), pp. 99-102.
  3. ^ Ellis TN and Kuehn MJ (2010) Virulence and immuno-modulatory roles of bacterial outer membrane vesicles. Microbiolgy and Molecular Biology Reviews, vol. 74 (no. 1), pp. 81-94.
  4. ^ Acevedo R, Fernandez S, Zayas C, Acosta D, Sarmiento ME, Ferro VA, Rosenquvist E, Campa C, Cardoso D, Garcia L and Perez JL (2014) Bacterial outer membrane vesicles and vaccine applications. Frontiers in Immunology, vol. 5:121.
  5. ^ Kulp A and Kuehn MJ (2010) Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annual Reviews of Microbiology, vol. 64, pp. 163-184.
  6. ^ YashRoy R C (2003) Eucaryotic cell intoxication by Gram-negative organisms: A novel bacterial outermembrane-bound nanovesicular model for Type-III secretion system. Toxicology International, vol. 10 (No. 1), 1-9.