Project description:Giardia duodenalis is a prevalent intestinal pathogens known to cause giardiasis, a condition characterized by diarrhea and frequently linked to malnutrition and growth impairments in children. The presence of Giardiavirus (GLV) in Giardia strains has been associated with heightened immune cytokine responses in the host compared to the GLV-free strains. However, the transmission mode and biological significance of GLV remain unclear. In this study, by using G. duodenalis DH (GLV-containing) and WBC6 (GLV-free) strains, we demonstrated that the DH strain produced extracellular vesicles (EVs), which originated from unique peripheral vesicle and bead-like structures in the ventrolateral flange. Nanoparticle tracking analysis revealed that GLV infected-G. duodenalis DH strain secreted fewer EVs than the GLV-free WBC6 strain. Biochemical and electron microscopy demonstrated that GLV virions can exploit the Giardia EVs pathway to facilitate their spread among parasites. Giardia uptake of GLV-containing EVs occured through clathrin-mediated endocytosis, leading to rapid infection of trophozoites by GLV. Furthermore, GLV infection enhanced messenger RNA translation efficiency, influencing protein abundance in Giardia trophozoites. The presence of GLV also upregulated the glycolytic pathway, with Giardia enolase closely associated with GLV replication. Importantly, Giardia infected with GLV alleviated the pathogenicity of parasite compared to the GLV-freeGiardia strain. These findings highlight the pivotal role of GLV in regulating Giardia biology, suggesting its potential for informing the development of novel intervention strategies against Giardia infections.
Project description:Giardia duodenalis is a protozoan parasite responsible for gastroenteritis in vertebrates, including humans. The prevalence of G. duodenalis is partly owed to its direct and simple life cycle, as well as the formation of the environmentally resistant and infective cysts. Several proteomic and transcriptomic studies have previously analysed global changes during the encystation process using the well-characterised laboratory isolate and genome strain, WBC6. To expand current comparative analyses, this study presents the first quantitative global study of encystation using pathogenically relevant and alternative assemblage A strains: the human-derived BRIS/82/HEPU/106 and avian-derived BRIS/95/HEPU/2041. We have utilised tandem MS/MS with a label-free quantitative approach to compare cysts and trophozoite life stages between strains for variation, as well as confirm universal encystation markers of Assemblage A.
