Cracking Open Bacterial Membrane Vesicles

Abstract

Membrane vesicles (MVs) are nanoparticles composed of lipid membranes that are produced by both Gram-negative and Gram-positive bacteria. MVs have been assigned diverse biological functions, and they show great potential for applications in various fields. However, the mechanisms underlying their functions and biogenesis are not completely understood. Accumulating evidence shows that MVs are heterogenous, and different types of MVs with different compositions are released from the same species. To understand the origin and function of these MVs, determining the biochemical properties of MVs is important. In this review, we will discuss recent progress in understanding the biochemical composition and properties of MVs.

Keywords: cargo selection; endocytosis; lipidome; membrane fusion; membrane vesicles; proteome.

FIGURE 1

Mechanisms of MV biogenesis. Several mechanisms underlying MV formation in bacteria have been proposed. In Gram-negative bacteria, outer membrane vesicles and outer-inner membrane vesicles are produced through outer membrane blebbing or explosive cell lysis. Outer membrane blebbing is induced by structural changes in the cell envelope, such as a decrease in outer membrane-peptidoglycan cross-linking proteins, intercalation of molecules [such as Pseudomonas Quinolone Signal (PQS)] in the membrane, or the accumulation of misfolded proteins at specific regions of the cell envelope. Explosive cell lysis is triggered by phage-derived endolysin, which degrades the cell wall. In Gram-positive bacteria, cytoplasmic membrane vesicles are produced through bubbling cell death, in which phage-derived endolysin degrades the cell wall and the cytoplasmic membrane protrudes through the resulting holes in the peptidoglycan. In mycolic acid-containing bacteria, the mechanism of MV formation remains unknown, although there is evidence that these bacteria produce MVs containing inner membrane lipids or cell envelope associated-proteins such as S-layer component proteins.

FIGURE 2

Routes of MV entry into mammalian and bacterial cells. In mammalian cells, bacterial MVs are thought to be internalized through several routes. Cholesterol-rich lipid rafts in the plasma membrane of the mammalian cell mediates MV entry through caveolin-mediated endocytosis or fusion of the lipid raft and bacterial MV. Clathrin-mediated endocytosis is also involved in MV internalization. In bacterial cells, two types of MV entry have been proposed: MV components, such as DNA, may be internalized into bacterial cells through type IV pili, or MVs may also fuse with the cellular membrane of the bacterial cell, depending on the membrane composition.