Gram-Negative Bacteria's Outer Membrane Vesicles

Abstract

Outer membrane vesicles (OMVs) are spherical bilayered nanoparticles derived from the outer layer of Gram-negative bacteria. Bacteria communicate with nearby bacteria, their environment, and the cells of their host by secreting OMVs, which are essential for their survival. OMVs also play a critical role in bacterial pathogenesis since they are loaded with virulence factors, toxins, and enzymes. OMVs may modulate the immune response of the host by initiating inflammation through cytokine production and activating the innate immune response. OMVs also contribute to the resistance of bacteria to antibiotics by carrying antibiotic-degrading enzymes and acting as natural protection barriers. Concerns have also been raised regarding OMVs mediating the transfer of antibiotic resistance. Due to their advantageous properties, OMVs are attractive platforms for vaccine discovery and drug delivery research. In this review, we discuss the fundamental structure and biogenesis mechanisms of OMVs as well as their multifaceted roles in bacterial infection pathogenesis and host immune responses. We also discuss application examples of OMVs.

Keywords: Gram-negative bacteria; Outer membrane vesicles; Pathogenesis; Virulence.

Figure 1. This figure depicts cell wall envelope of the Gram-negative bacteria and biogenesis of Outer membrane vesicles (OMV). Gram-negative bacteria consists of two membrane. Outer leaflet of the outer membrane (OM) is composed of lipopolysaccharide (LPS). To stabilize membrane integrity, Braun's lipoprotein in the OM crosslinks OM layer and peptidoglycan (PG). Also Outer membrane protein A non-covalently binds with PG layer. The Tol-Pal complex which is consisted with cytoplasmic proteins, periplasmic protein, and outer membrane lipoprotein (peptidoglycan-associated lipoprotein) binds cell wall envelope together. OMV is generated from the OM by several mechanisms including reducing cell wall envelope crosslinks, LPS remodeling, and bilayer couple model by increasing OM fluidity. Periplasmic proteins including various virulence factors and cellular waste such as misfolded proteins are packaged into OMVs as cargos and secreted.

Figure 2. Transmission electron microscope-images of purified outer membrane vesicles derived from clinical isolates of Pseudomonas aeruginosa with magnification of × 80,000.