Table 2.

Differences and similarities in EVs deriving from eukaryotic cells and bacteria

Eukaryotic Organism	Bacteria
Spherical particles with a size range from 30 to 100 nm (exosomes), 100–1000 nm (MVs) or 500–2000 nm (apoptotic bodies) Stable at 37 °C for 24 h. Sensitive to high temperature but stable in the frozen and freeze-dried states [204]	Spherical particles with a size range from 10 to 400 nm. The maximum size is smaller than eukaryotic EVs due to smaller sized bacterial cells Stable at 37 °C for 24 h. Greater tolerance to hot temperatures [205]. Stable in the frozen and freeze-dried states
Exosomes are commonly enriched in endosome-associated proteins	Mainly composed of proteins and phospholipids of the outer membrane
Exosomes and MVs are released by healthy and damaged cells. Apoptotic bodies are released by dying cells on an apoptotic pathway	All Gram-negative bacteria produce outer membrane vesicles (OMVs) and possibly also all Gram-positive bacteria. Gram-negative bacteria can produce specific vesicles with a double layer using both the outer and inner membranes
Originates in the plasma membrane except exosomes, which are made by the endocytic pathway	Bacteria Gram-negative and Gram-positive have a different mechanism of vesicle formation due to their distinct membrane structure, which originates in the membrane
They are released from cells by a variety of mechanisms depending on their mode of biogenesis and they are not released homogeneously by the membrane	Production is not uniformly distributed along the bacteria surface but there are “hot spots”
High heterogeneity in the composition of the surface and the interior	High heterogeneity in the composition of the surface and the interior
There are universal markers such as CD40 for microvesicles or flotillin for exosomes	There are no universal markers for their identification due to their diversity
EVs can contain different RNAs such as miRNA or mRNA but it is unusual for them to carry DNA	EVs can contain genetic material and participate in horizontal gene transfer
Harmful cells such as tumor cells present EVs with specific and useful contents for their survival	In pathogenic bacteria, specific molecules have been found such as adhesins, toxins and/or immunomodulatory compounds as cargo of OMVs
The main function is intercellular communication, except for apoptotic bodies, which facilitates phagocytosis	They are more relevant as a mechanism to carry away toxic compounds for bacteria than in eukaryotic cells
Production depends on the cell type and its physiology state	Their production increases as a response to environmental stress
A non-spontaneous biological process	A non-spontaneous biological process