Update on relevant trypanosome peptidases: Validated targets and future challenges

Álvarez, Vanina E.; Iribarren, Paula Ana; Niemirowicz, Gabriela T.; Cazzulo, Juán José

doi:10.1016/j.bbapap.2020.140577

Cited by 16 publications

(14 citation statements)

References 245 publications

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“…Proteases are known pathogenic factor of T. cruzi , some of which are implicated as drug targets ( 37 ). Some proteases are expressed throughout all life cycle stages, and others are differentially expressed ( 38 ). In amastigote stage, cruzipain 2, an isoform of the major cysteine protease cruzain, is localized on the cell surface ( 39 , 40 ).…”

Section: Discussionmentioning

confidence: 99%

Differentiating Trypanosoma cruzi in a Host Mammalian Cell Imaged in Aqueous Liquid by Atmospheric Scanning Electron Microscopy

et al. 2022

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Using Atmospheric Scanning Electron Microscopy (ASEM), we visualized interaction between infectious stage of Trypanosoma cruzi and completely intact host mammalian cell. Plasma membrane appears translucent under ASEM, which not only enables direct observation of T. cruzi within its host cell, but also reveals internal structures of the parasite itself.

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Section: Discussionmentioning

confidence: 99%

Differentiating Trypanosoma cruzi in a Host Mammalian Cell Imaged in Aqueous Liquid by Atmospheric Scanning Electron Microscopy

et al. 2022

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“…It should be noted that DPPI is, by no means, ubiquitous in eukaryotes, as it is absent in some major evolutionary groups such as plants and fungi, as discussed in [1,27]. For example, it is also absent in trypanosomes, which are otherwise well known for their papain-like and other peptidases [28].…”

Section: Discussionmentioning

confidence: 99%

Evolutionary Analysis of Dipeptidyl Peptidase I

Varda

Novinec

2022

IJMS

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Human dipeptidyl peptidase I (DPPI) belongs to the family of papain-like cysteine peptidases. Its distinctive features are the unique exclusion domain which enables the eponymous activity and homotetramerization of DPPI, and its dependence on chloride ions for enzymatic activity. The oligomeric state of DPPI is unique in this family of predominantly monomeric peptidases. However, a distant DPPI ortholog from Plasmodium falciparum has been shown to be monomeric, indicating that the oligomeric state of DPPI varies between lineages. The aim of this work was to study the evolution of DPPI, with particular attention to the structural features that determine its characteristic enzymatic activity and preferences, and to reconstruct the evolution of its oligomerization. We analyzed fifty-seven selected sequences of DPPI and confirmed its presence in three lineages, namely, Amorphea (including animals and Amoebozoa), Alveolates and the metamonad Giardia. The amino acid residues that bind the chloride ion are highly conserved in all species, indicating that the dependence on chloride ions for activity is an evolutionarily conserved feature of DPPI. The number of N-glycosylation sites is significantly increased in animals, particularly vertebrates. Analysis of homology models and subunit contacts suggests that oligomerization is likely restricted to DPPIs in the Amorphea group.

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“…3.4.22.15) enzymes, based on pro-domain sequences and length. 75 , 76 Cysteine proteases (CPs) are recognized as virulence factors in Giardia, their exact role in the disease’s molecular pathogenesis remains unknown. The goal of this study was to describe the three primary secreted CPs (CP14019, CP16160, and CP16779), which were discovered in the medium during interaction with intestinal epithelial cells (IECs) in vitro using mass spectrometry.…”

Section: Helicobacter Pylori Pathogenicity Islands and Giardia Lamblia Cysteine Proteases In Role Of Coinfectmentioning

confidence: 99%

Helicobacter pylori Pathogenicity Islands and Giardia lamblia Cysteine Proteases in Role of Coinfection and Pathogenesis

Tilahun¹,

Gedefie²,

Belayhun³

et al. 2022

IDR

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Helicobacter pylori is a well-known human-specific stomach pathogen that infects more than half of the world's population. The infection with this bacterium can cause a variety of gastrointestinal problems, including chronic gastritis, peptic ulcers, and even cancer. H. pylori is a highly infectious bacterium. H. pylori causes an increase in gastric mucosa pH or gastric mucosa intestinal metaplasia. These modifications in the stomach environment are necessary for G. lamblia colonization to occur. Giardia lamblia is a flagellate protozoan parasite that can cause giardiasis in humans and other mammals. It dwells in the duodenum and upper jejunum. Globally, over 280 million cases of human giardiasis are predicted to occur each year. Simultaneous human colonization by G. lamblia and H. pylori is a typical occurrence since the viruses' predisposing factors are similar in both groups. Giardiasis is a parasitic infection that affects both children and adults worldwide. Infection with Giardia is more common in underdeveloped countries. Globally, more than 200 million cases of giardiasis are detected each year. In contrast, the presence of G. lamblia in the host body triggers an immunological response comparable to that of H. pylori, with lymphocytes strongly polarized towards Th1. As a result, their combined presence exacerbates host tissue damage. The major goal of this seminar is to describe the pathophysiology, immunology, and clinical aspects of G. lamblia and H. pylori coinfection using a comprehensive search of PubMed, Lancet, and Google Scholar sources. Upper gastrointestinal problems such as upper abdominal pain, abdominal bloating, nausea, vomiting, epigastric pain/burning, and belching are all caused by both organisms. Differentiation by physical examination is impossible in people infected with both bacteria. For this coinfection distinction, a laboratory diagnosis is required. G. lamblia and H. pylori, when present together, have a synergistic effect on the host and can cause serious damage. As a result, researchers should delve deeper into the mechanics underlying this potential microbial interaction.

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Update on relevant trypanosome peptidases: Validated targets and future challenges

Cited by 16 publications

References 245 publications

Differentiating Trypanosoma cruzi in a Host Mammalian Cell Imaged in Aqueous Liquid by Atmospheric Scanning Electron Microscopy

Differentiating Trypanosoma cruzi in a Host Mammalian Cell Imaged in Aqueous Liquid by Atmospheric Scanning Electron Microscopy

Evolutionary Analysis of Dipeptidyl Peptidase I

Helicobacter pylori Pathogenicity Islands and Giardia lamblia Cysteine Proteases in Role of Coinfection and Pathogenesis

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