| Abstract | Giardia intestinalis is an anaerobic protozoan that is an important etiologic agent of inflammation-drive diarrhea worldwide. Although self-limiting, a deep understanding of its multifactorial pathogenicity is unknown, like the disruption of the intestinal barrier. There is evidence that the parasite is capable of shedding extracellular vesicles (EVs) under diverse conditions, where it could modulate the physiopathology of giardiasis. Here we describe new insights of G. intestinalis EV production, revealing its capacity to shed two different enriched EV populations (large extracellular and small extracellular vesicles) and identified a relevant adhesion function associated only with the larger population. Our work also aimed to assess the influence of two recently identified inhibitors of EV release in mammalian cells, namely peptidylarginine deiminase (PAD) inhibitor and Cannabidiol (CBD), on EV release from Giardia and putative effects on hostpathogen interactions. PAD inhibitor Cl-amidine and CBD were both able to effectively reduce EV shedding, the PAD-inhibitor specifically affecting release of large extracellular vesicles and interfering with an in vitro host-pathogen interactions. The strong efficacy of PAD-inhibitor on Giardia EV release indicates a phylogenetically conserved pathway of PAD-mediated EV release, most likely affecting the Giardia arginine deiminase (GiADI) homolog of mammalian PADs. While there is still much to learn about G. intestinalis interaction with its host, our results suggests that large and small EVs may be differently involved in protozoa communication, and that EV-inhibitor treatment may be a novel strategy for recurrent giardiasis treatment |
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