Extracellular Vesicles from the Protozoa Acanthamoeba castellanii: Their Role in Pathogenesis, Environmental Adaptation and Potential Applications

Abstract

Extracellular vesicles (EVs) are membranous compartments of distinct cellular origin and biogenesis, displaying different sizes and include exosomes, microvesicles, and apoptotic bodies. The EVs have been described in almost every living organism, from simple unicellular to higher evolutionary scale multicellular organisms, such as mammals. Several functions have been attributed to these structures, including roles in energy acquisition, cell-to-cell communication, gene expression modulation and pathogenesis. In this review, we described several aspects of the recently characterized EVs of the protozoa Acanthamoeba castellanii, a free-living amoeba (FLA) of emerging epidemiological importance, and compare their features to other parasites’ EVs. These A. castellanii EVs are comprised of small microvesicles and exosomes and carry a wide range of molecules involved in many biological processes like cell signaling, carbohydrate metabolism and proteolytic activity, such as kinases, glucanases, and proteases, respectively. Several biomedical applications of these EVs have been proposed lately, including their use in vaccination, biofuel production, and the pharmaceutical industry, such as platforms for drug delivery.

Isolation of Acanthamoeba T5 from Water: Characterization of Its Pathogenic Potential, Including the Production of Extracellular Vesicles

“…Besides, in Dictyostelium discoideum, another free-living amoeba, the results of several studies raised the hypothesis of the participation of EVs in cell-to-cell communication [48,49]. Regarding Acanthamoeba, as mentioned before, there are two recent studies that demonstrated the production of EVs by trophozoytes of A. castellanii under homeostasis and nutritional stress and characterized their protein content [34,35]. The authors determined the lipid and protein content of these vesicles secreted by the amoebae incubated at 28 • C, temperature in which amoebae behave as free-living organisms.…”

“…Except for the population of 50.29 ± 8.49 nm, the size of the EVs obtained in both cases was similar to those reported in the two previous published studies to date, although these were performed using Acanthamoeba of the genotype T4. For example, in 2018, de Souza Gonçalves et al [34] reported EVs of Acanthamoeba castellanii of 117.1 ± 73.3 nm in amoebae incubated in PYG medium and EVs of Acanthamoeba castellanii of 117.7 ± 55.8 nm in amoebae incubated in a glucose medium (under nutritional stress). More recently, Lin et al [35] reported mean diameters of 166.7 nm in the EVs of the same strain of Acanthamoeba.…”

“…The authors determined the lipid and protein content of these vesicles secreted by the amoebae incubated at 28 • C, temperature in which amoebae behave as free-living organisms. De Souza Gonçalves et al [34] proposed that the EVs in FLA could participate in the regulation of their surrounding environment, including the amoebic population density and the regulation of symbiontsǵ ene expression. It was also suggested that EVs could play a role during the infection process of the amoebae to a host and that they could also induce the immune response in human cells [35].…”

“…Besides intercellular communication and pathogenesis, EVs have been involved in immunomodulation, evasion of the immune response and metastasis, among others. In the case of protozoan parasites, they have been described specially in Trypanosoma cruzi [23][24][25], Leishmania [26,27], Toxoplasma gondii [28,29], Eimeria tenella [30], Cryptosporidium parvum [31], Trichomonas vaginalis [32], Giardia intestinalis [33] and recently, in Acanthamoeba castellanii, a free-living amoeba [34,35].…”

Perils and Promises of Pathogenic Protozoan Extracellular Vesicles

“…The study of parasitic protozoa began in the 17th century (Cox, 2002 ) and, at the least, there are about 90 etiologic species of important human parasitic diseases (Coakley et al, 2015 ), while several other species affect economically important animals (Taylor, 2000 ). Pathogenic and amphizoic protozoa (Gonçalves and Ferreira, 2019 ) are dispersed within phyla amoeba, apicomplexa, metamonada, parabasalia and kinetoplastida (Szempruch et al, 2016a ), which are known to cause a wide range of important diseases such as amoebiasis, malaria, babesiosis, toxoplamosis, leishmaniasis, trypanosomiasis, cryptosporidiosis, trichomoniasis, giardiasis, neosporosis, theileriosis, etc. Over the years, there have been continuous investigations on protozoan parasites' sub-cellular components, organellar structures, secretory/excretory molecules, and, recently, extracellular vesicles (Yanez-Mo' et al, 2015 ).…”