Biogenesis and Biological Functions of Extracellular Vesicles in Cellular and Organismal Communication With Microbes

Abstract

Extracellular vesicles (EVs) represent a prominent mechanism of transport and interaction between cells, especially microbes. Increasing evidence indicates that EVs play a key role in the physiological and pathological processes of pathogens and other symbionts. Recent research has focused on the specific functions of these vesicles during pathogen-host interactions, including trans-kingdom delivery of small RNAs, proteins and metabolites. Much current research on the function of EVs is focused on immunity and the interactions of microbes with human cells, while the roles of EVs during plant-microbe interactions have recently emerged in importance. In this review, we summarize recent research on the biogenesis of these vesicles and their functions in biology and pathology. Many key questions remain unclear, including the full structural and functional diversity of EVs, the roles of EVs in communication among microbes within microbiomes, how specific cargoes are targeted to EVs, whether EVs are targeted to specific destinations, and the full scope of EVs' transport of virulence effectors and of RNA and DNA molecules.

Keywords: biogenesis; cell to cell communication; extracellular vesicles (EVs); pathogen-plant interaction; pathology.

FIGURE 1

Extracellular vesicles produced by bacteria and archaea. (A) Gram-negative eubacteria release outer membrane vesicles (OMVs) by budding. A similar process results in the formation of outer-inner membrane vesicles (O-IMVs), with remodeling of the cell wall. Cell lysis induced by phage or environmental stress can also release O-IMVs and explosive OMVs (E-OMVs). It is unknown if similar processes occur in the small number of diderm archaeal species. (B) In gram-positive eubacteria and monoderm Euryarcheota, cytoplasmic membrane vesicles (CMVs) are released via cell membrane budding and cell wall re-modeling or as the result of cell lysis where the vesicles are extruded through gaps in the rigid cell wall. In the Crenarcheaota, CMVs are released via the action of the archaeal ESCRT machinery. See also Table 1.

FIGURE 2

Different kinds of extracellular vesicles produced across diverse eukaryotic kingdoms. (I) Microvesicles are produced directly by pinching off of the plasma membrane. (II) Exosomes are produced through the intermediate structure of multivesicular bodies. (III) Apoptosis results in apoptotic bodies that constitute another type of extracellular vesicle. In plants and fungi, extracellular vesicles must cross a cell wall.

FIGURE 3

Multivesicular body pathways of exosome formation and release in mammals, plants and fungi. Commonalities, differences and unknowns are shown in the machinery by which exosomes are formed via multivesicular bodies (MVBs). Machinery which differs is indicated with colored text. Orange bars indicate fusion of MVBs with the plasma membrane. “?” indicates machinery that has not yet been well defined.

FIGURE 4

Endosomal sorting complex required for transport (ESCRT) machinery in plants compared to that in mammals and fungi. The process of loading ubiquitinated membrane cargoes into exosomes is shown. Ub, ubiquitin; PI3P, phosphatidylinositol-3-phosphate; ADP, adenosine diphosphate; Pi, phosphate. All other entities shown are protein components of the ESCRT machinery. The first step in the plant pathway is not well described.

FIGURE 5

Extracellular vesicle functions during infection by the malaria parasite Plasmodium falciparum. During infection P. falciparum EVs may trigger host inflammatory responses or manipulate gene expression to reduce host barriers to infection. P. falciparum EVs may also mediate communication among parasite cells to regulate transmission stage production or even transfer antibiotic resistance.

FIGURE 6

Extracellular vesicle roles in interactions of plants with fungi and oomycetes. Plants and their eukaryotic pathogens exchange EVs during infection. Plant EVs carrying Tetraspanin8 (Tet8) but lacking syntaxin PEN1 (TET8+ PEN1– EVs) carry small RNAs (sRNAs) and other defense compounds including small molecules, enzymes and other proteins. The specific role of plant TET8-negative PEN1-positive (TET– PEN1+) EVs remains unclear. Some of those molecules may enter the pathogen cytoplasm or the nucleus where sRNAs may bind to pathogen RNA-induced silencing complexes (RISC); some enzymes such as callose synthase may be targeted to papillae to strengthen cell wall defenses against pathogen invasion. Pathogen EVs may carry sRNAs as well as other virulence compounds, possibly including some effectors. sRNAs may target plant RISC complexes. MVBs, multivesicular bodies; PRR, pattern recognition receptor; BAK1, BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1; SOBIR1, suppressor of BRASSINOSTEROID INSENSITIVE 1 (BRI1)-associated kinase (BAK1)-interacting receptor kinase 1.