Peptidylarginine Deiminase inhibition abolishes the production of large extracellular vesicles from Giardia intestinalis, affecting host-pathogen interactions by hindering adhesion to host cells

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