Role of cytoneme-like structures and extracellular vesicles inTrichomonas vaginalisparasite: parasite communication

Trichomonas vaginalis, the etiologic agent of the most common non-viral sexually transmitted infection worldwide, colonizes the human urogenital tract where it remains extracellular and adheres to epithelial cells. With an estimated prevalence of 276 million new cases annually, mixed infections with different parasite strains are expected. Although it is considered as obvious that parasites interact with their host to enhance their own survival and transmission, evidence of mixed infection call into question the extent to which unicellular parasites communicate with each other. Here, we demonstrated that differentT. vaginalisstrains are able to communicate through the formation of cytoneme-like membranous cell connections. We showed thatT. vaginalisadherent strains form abundant membrane protrusions and cytonemes formation of an adherent parasite strain (CDC1132) is affected in the presence of a different strain (G3 or B7RC2). Using a cell culture inserts assays, we demonstrated that the effect in cytoneme formation is contact independent and that extracellular vesicles (EVs) are responsible, at least in part, of the communication among strains. In this sense, we found that EVs isolated from G3, B7RC2 and CDC1132 strains contain a highly distinct repertoire of proteins, some of them involved in signaling and communication, among other functions. Finally, we showed that parasite adherence to host cells is affected by this communication between strains as binding of adherentT. vaginalisCDC1132 strain to prostate cells is significantly higher in the presence of G3 or B7RC2 strains. Demonstrating that interaction of isolates with distinct phenotypic characteristics may have significant clinical repercussions, we also observed that a poorly adherent parasite strain (G3) adheres more strongly to prostate cells in the presence of an adherent strain. The study of signaling, sensing and cell communication in parasitic organisms will surely enhance our understanding of the basic biological characteristics of parasites that might have important consequences in pathogenesis.