Peptidylarginine Deiminase Inhibition Abolishes the Production of Large Extracellular Vesicles FromGiardia intestinalis, Affecting Host-Pathogen Interactions by Hindering Adhesion to Host Cells

Author(s)

Gavinho, Bruno ^[1] ; Sabatke, Bruna ^[2] ; Feijoli, Veronica ^[3] ; Rossi, Izadora Volpato ^[2] ; da Silva, Janaina Macedo ^[3] ; Evans-Osses, Ingrid ^[4] ; Palmisano, Giuseppe ^[3] ; Lange, Sigrun ^[5] ; Ramirez, Marcel Ivan ^{[6, 7]}

Affiliation

^[1] Univ Fed Parana, Programa Posgrad Microbiol Parasitol & Patol, Dept Patol, Curitiba, Parana - Brazil

^[2] Univ Fed Parana, Dept Biol Celular, Programa Posgrad Biol Celular & Mol, Curitiba, Parana - Brazil

^[3] Univ Sao Paulo, Inst Ciencias Biomed 2, Dept Parasitol, Sao Paulo - Brazil

^[4] Ctr Univ Santa Cruz, Dept Enfermagem, Curitiba, Parana - Brazil

^[5] Univ Westminster, Sch Life Sci, Tissue Architecture & Regenerat Res Grp, London - England

^[6] Univ Fed Parana, Dept Bioquim & Biol Mol, Curitiba, Parana - Brazil

^[7] Inst Oswaldo Cruz, Rio De Janeiro - Brazil

• Document type: Journal article
• Source: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 10, SEP 23 2020.
• Web of Science Citations: 1

Abstract

Giardia intestinalisis a microaerophilic protozoan that is an important etiologic agent of diarrhea worldwide. There is evidence that under diverse conditions, the parasite is capable of shedding extracellular vesicles (EVs) which modulate the physiopathology of giardiasis. Here we describe new features ofG. intestinalisEV production, revealing its capacity to shed two different enriched EV populations: large (LEV) and small extracellular vesicles (SEV) and identified relevant adhesion functions associated with the larger population. Proteomic analysis revealed differences in proteins relevant for virulence and host-pathogen interactions between the two EV subsets, such as cytoskeletal and anti-oxidative stress response proteins in LEVS. We assessed the effect of two recently identified inhibitors of EV release in mammalian cells, namely peptidylarginine deiminase (PAD) inhibitor and cannabidiol (CBD), on EV release fromGiardia. The compounds were both able to effectively reduce EV shedding, the PAD-inhibitor specifically affecting the release of LEVs and reducing parasite attachment to host cellsin vitro. Our results suggest that LEVs and SEVs have a different role in host-pathogen interaction, and that treatment with EV-inhibitors may be a novel treatment strategy for recurrent giardiasis. (AU)

• FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
• Grantee: Giuseppe Palmisano
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 18/18257-1 - Multi-user equipment approved in grant 14/06863-3: HPLC system configured for analysis of carbohydrates, amino acidis, peptides and glycoproteins
• Grantee: Giuseppe Palmisano
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 14/06863-3 - Post-translational modifications in cancer and parasite infection diagnosis: methodological approaches and biological implications
• Grantee: Giuseppe Palmisano
• Support Opportunities: Research Grants - Young Investigators Grants