The proteasome of the differently-diverged eukaryote Giardia lamblia and its role in remodeling of the microtubule-based cytoskeleton

Abstract

Giardia lamblia is the causative agent of the diarrheal disease giardiasis, against which only a limited number of drugs are currently available. Increasing reports of resistance to these drugs makes it necessary to identify new cellular targets for designing the next generation of anti-giardial drugs. Towards this goal, therapeutic agents that target the parasitic cellular machinery involved in the functioning of the unique microtubule-based cytoskeleton of the Giardia trophozoites are likely to be effective as microtubule function is not only important for the survival of trophozoites within the host, but also their extensive remodeling is necessary during the transition from trophozoites to cysts. Thus, drugs that affect microtubule remodeling have the potential to not only kill the disease-causing trophozoites, but also inhibit transmission of cysts in the community. Recent studies in other model organisms have indicated that the proteasome plays an integral role in the formation and remodeling of the microtubule-based cytoskeleton. This review draws attention to the various processes by which the giardial proteasome may impact the functioning of its microtubule cytoskeleton and highlights the possible differences of the parasitic proteasome and some of other cellular machinery involved in microtubule remodeling, compared to that of the higher eukaryotic host.

Polyphenolic extract from Punica granatum peel causes cytoskeleton-related damage on Giardia lamblia trophozoites in vitro

“…Due to their importance, alterations in proteins or cytoskeletal elements in the parasite can lead to cellular damage, alteration of attachment, and ultimately cell death. Several phytochemicals have demonstrated their antiparasitic effects through alteration of cellular elements essential for this pathogen survival ( Ray & Sarkar, 2017 ; Wink, 2012 ). In our study, we analyzed the effect of polyphenols in pomegranate peel ethanolic extract on G. lamblia trophozoites in vitro .…”

A new gene inventory of the ubiquitin and ubiquitin-like conjugation pathways in Giardia intestinalis

“…The proteasome components have recently been analysed using bioinformatics, confirming findings reported earlier where a remarkable conservation was observed. (7) Previous studies have identified three genes for Ub, one E1 enzyme, 11 E2 enzymes, four E3 ligases, and 9 DUBs; (8,9,10,11,12,13) however, the most divergent genes may have been overlooked. Herein, we performed an exhaustive search using an intelligent systems approach based on hidden Markov models (HMMs) with profiles from the Pfam and Superfamily databases.…”