Exosome secretion affects social motility in Trypanosoma brucei

Abstract

Extracellular vesicles (EV) secreted by pathogens function in a variety of biological processes. Here, we demonstrate that in the protozoan parasite Trypanosoma brucei, exosome secretion is induced by stress that affects trans-splicing. Following perturbations in biogenesis of spliced leader RNA, which donates its spliced leader (SL) exon to all mRNAs, or after heat-shock, the SL RNA is exported to the cytoplasm and forms distinct granules, which are then secreted by exosomes. The exosomes are formed in multivesicular bodies (MVB) utilizing the endosomal sorting complexes required for transport (ESCRT), through a mechanism similar to microRNA secretion in mammalian cells. Silencing of the ESCRT factor, Vps36, compromised exosome secretion but not the secretion of vesicles derived from nanotubes. The exosomes enter recipient trypanosome cells. Time-lapse microscopy demonstrated that cells secreting exosomes or purified intact exosomes affect social motility (SoMo). This study demonstrates that exosomes are delivered to trypanosome cells and can change their migration. Exosomes are used to transmit stress signals for communication between parasites.

The low complexity regions in the C-terminus are essential for the subcellular localisation of Leishmania casein kinase 1 but not for its activity

“…As shown Figure 2E (CK1.2-V5, white arrow), CK1.2-V5 is detected in the flagellar pocket (FP), which is important for processes such as exo/endocytosis or flagellum assembly [31]. The FP is also one of the sites of exosome excretion in Trypanosoma brucei [32]. Exosomes are vesicles of endosomal origin released by cells from multi-vesicular bodies into their extracellular environment and known to promote cell-to-cell communications [33].…”

Extracellular Vesicles: A Prevalent Tool for Microbial Gene Delivery?

“…For clarification, in this manuscript, we will refer to all vesicles secreted by prokaryotic microbes as MVs. Similarly to their prokaryote counterparts, eukaryotic microbes also release several types of vesicles, termed extracellular vesicles (EVs), such as exosomes, which originate from the endosomal compartment, and microvesicles, which are shed from the plasma membrane . It has recently been revealed that, in addition to RNA and proteins, vesicles from different eukaryotic systems also harbor DNA molecules.…”

“…Stress conditions are not only able to induce vesicle shedding but also prompt vesicular cargo ‘upgrade’ to facilitate an improved response. One of the greatest challenges confronted by microorganisms is stress induced by antimicrobial treatments, a threat that can be overcome by the development of drug resistance.…”

Exosomes in the Pathogenic Protozoan Trypanosoma Cruzi

“…Studies of Leishmania [30,31], Trypanosoma brucei [32,33] and Plasmodium [34] have clearly shown that these parasites also produce microvesicles that are released into the intercellular space or the bloodstream. Exosomes secreted by P. falciparum are directly related to the infection of red blood cells in a mechanism that seems to be important for the parasite's transmission to the insect vector [34].…”