Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract, where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Despite the serious consequences associated with trichomoniasis disease, little is known about parasite or host factors involved in attachment of the parasite-to-host epithelial cells. Here, we report the identification of microvesicle-like structures (MVs) released by T. vaginalis. MVs are considered universal transport vehicles for intercellular communication as they can incorporate peptides, proteins, lipids, miRNA, and mRNA, all of which can be transferred to target cells through receptor-ligand interactions, fusion with the cell membrane, and delivery of a functional cargo to the cytoplasm of the target cell. In the present study, we demonstrated that T. vaginalis release MVs from the plasma and the flagellar membranes of the parasite. We performed proteomic profiling of these structures demonstrating that they possess physical characteristics similar to mammalian extracellular vesicles and might be selectively charged with specific protein content. In addition, we demonstrated that viable T. vaginalis parasites release large vesicles (LVs), membrane structures larger than 1 µm that are able to interact with other parasites and with the host cell. Finally, we show that both populations of vesicles present on the surface of T vaginalis are induced in the presence of host cells, consistent with a role in modulating cell interactions.
BackgroundToxoplasmosis is a worldwide infection caused by the protozoan parasite Toxoplasma gondii, which causes chorioretinitis and neurological defects in congenitally infected newborns or immunodeficient patients. The efficacy of the current treatment is limited, primarily by serious host toxicity. In recent years, research has focused on the development of new drugs against T. gondii. β-Carbolines (βCs), such as harmane, norharmane and harmine, are a group of naturally occurring alkaloids that show microbicidal activity. In this work, harmane, norharmane and harmine were tested against T. gondii.FindingsThe treatment of extracellular tachyzoites with harmane, norharmane and harmine showed a 2.5 to 3.5-fold decrease in the invasion rates at doses of 40 μM (harmane and harmine) and 2.5 μM (norharmane) compared with the untreated parasites. Furthermore, an effect on the replication rate could also be observed with a decrease of 1 (harmane) and 2 (norharmane and harmine) division rounds at doses of 5 to 12.5 μM. In addition, the treated parasites presented either delayed or no monolayer lysis compared with the untreated parasites.ConclusionsThe three βC alkaloids studied (norharmane, harmane and harmine) exhibit anti-T. gondii effects as evidenced by the partial inhibition of parasite invasion and replication. A dose–response effect was observed at a relatively low drug concentration (< 40 μM), at which no cytotoxic effect was observed on the host cell line (Vero).
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