scholarly journals The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Viviane Corrêa Santos ◽  
Antonio Edson Rocha Oliveira ◽  
Augusto César Broilo Campos ◽  
João Luís Reis-Cunha ◽  
Daniella Castanheira Bartholomeu ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Active Sites ◽  
Protozoan Parasite ◽  
Cysteine Proteases ◽  
Gene Repertoire ◽  
Parasite Life Cycle ◽  
Sequence Variations ◽  
Multigenic Family ◽  
Parasite Strains

AbstractCruzipains are the main papain-like cysteine proteases of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. Encoded by a multigenic family, previous studies have estimated the presence of dozens of copies spread over multiple chromosomes in different parasite strains. Here, we describe the complete gene repertoire of cruzipain in three parasite strains, their genomic organization, and expression pattern throughout the parasite life cycle. Furthermore, we have analyzed primary sequence variations among distinct family members as well as structural differences between the main groups of cruzipains. Based on phylogenetic inferences and residue positions crucial for enzyme function and specificity, we propose the classification of cruzipains into two families (I and II), whose genes are distributed in two or three separate clusters in the parasite genome, according with the strain. Family I comprises nearly identical copies to the previously characterized cruzipain 1/cruzain, whereas Family II encompasses three structurally distinct sub-types, named cruzipain 2, cruzipain 3, and cruzipain 4. RNA-seq data derived from the CL Brener strain indicates that Family I genes are mainly expressed by epimastigotes, whereas trypomastigotes mainly express Family II genes. Significant differences in the active sites among the enzyme sub-types were also identified, which may play a role in their substrate selectivity and impact their inhibition by small molecules.

scholarly journals The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites

2021 ◽  
Author(s):  
Viviane Corrêa Santos ◽  
Antonio Edson Rocha Oliveira ◽  
Augusto César Broilo Campos ◽  
João Luís Reis-Cunha ◽  
Daniella Castanheira Bartholomeu ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Active Sites ◽  
Protozoan Parasite ◽  
Cysteine Proteases ◽  
Gene Repertoire ◽  
Parasite Life Cycle ◽  
Sequence Variations ◽  
Multigenic Family ◽  
Parasite Strains

Abstract Cruzipains are the main papain-like cysteine proteases of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. Encoded by a multigenic family, previous studies have estimated the presence of dozens of copies spread over multiple chromosomes in different parasite strains. Here, we describe the complete gene repertoire of cruzipain in three parasite strains, their genomic organization, and expression pattern throughout the parasite life cycle. Furthermore, we have analyzed primary sequence variations among distinct family members as well as structural differences between the main groups of cruzipains. Based on phylogenetic inferences and residue positions crucial for enzyme function and specificity, we propose the classification of cruzipains into two families (I and II), whose genes are distributed in two or three separate clusters in the parasite genome, according with the strain. Family I comprises nearly identical copies to the previously characterized cruzipain 1/cruzain, whereas Family II encompasses three structurally distinct sub-types, named cruzipain 2, cruzipain 3, and cruzipain 4. RNA-seq data derived from the CL Brener strain indicates that Family I genes are mainly expressed by epimastigotes, whereas trypomastigotes mainly express Family II genes. Significant differences in the active sites among the enzyme sub-types were also identified, which may play a role in their substrate selectivity and impact their inhibition by small molecules.

scholarly journals The Intestinal Protozoan Parasite Entamoeba histolytica Contains 20 Cysteine Protease Genes, of Which Only a Small Subset Is Expressed during In Vitro Cultivation

2003 ◽  
Vol 2 (3) ◽  
pp. 501-509 ◽  
Author(s):  
Iris Bruchhaus ◽  
Brendan J. Loftus ◽  
Neil Hall ◽  
Egbert Tannich
Keyword(s):  
Entamoeba Histolytica ◽  
Cysteine Protease ◽  
Cathepsin L ◽  
Protozoan Parasite ◽  
Cysteine Proteases ◽  
Small Subset ◽  
In Vitro Cultivation ◽  
Intestinal Protozoan ◽  
Parasite Life Cycle

ABSTRACT Cysteine proteases are known to be important pathogenicity factors of the protozoan parasite Entamoeba histolytica. So far, a total of eight genes coding for cysteine proteases have been identified in E. histolytica, two of which are absent in the closely related nonpathogenic species E. dispar. However, present knowledge is restricted to enzymes expressed during in vitro cultivation of the parasite, which might represent only a subset of the entire repertoire. Taking advantage of the current E. histolytica genome-sequencing efforts, we analyzed databases containing more than 99% of all ameba gene sequences for the presence of cysteine protease genes. A total of 20 full-length genes was identified (including all eight genes previously reported), which show 10 to 86% sequence identity. The various genes obviously originated from two separate ancestors since they form two distinct clades. Despite cathepsin B-like substrate specificities, all of the ameba polypeptides are structurally related to cathepsin L-like enzymes. None of the previously described enzymes but 7 of the 12 newly identified proteins are unique compared to cathepsins of higher eukaryotes in that they are predicted to have transmembrane or glycosylphosphatidylinositol anchor attachment domains. Southern blot analysis revealed that orthologous sequences for all of the newly identified proteases are present in E. dispar. Interestingly, the majority of the various cysteine protease genes are not expressed in E. histolytica or E. dispar trophozoites during in vitro cultivation. Therefore, it is likely that at least some of these enzymes are required for infection of the human host and/or for completion of the parasite life cycle.

scholarly journals Transcriptome analysis of alternative splicing in the pathogen life cycle in human foreskin fibroblasts infected with Trypanosoma cruzi

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hyeim Jung ◽  
Seonggyun Han ◽  
Younghee Lee
Keyword(s):  
Life Cycle ◽  
Alternative Splicing ◽  
Trypanosoma Cruzi ◽  
Exon Skipping ◽  
Protozoan Parasite ◽  
Rna Seq ◽  
Parasite Life Cycle ◽  
Human Foreskin Fibroblasts ◽  
Insight Into ◽  
Intracellular Protozoan Parasite

Abstract Trypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease as a zoonotic pathogen. The parasite has been shown to remodel expression in the host transcriptome under different conditions. Although alternative splicing (AS) is involved in virtually every biological function in eukaryotes, including cellular differentiation and responses to immune reactions, host AS events that occur as a result of T. cruzi infection have yet to be explored. In this study, we bioinformatically investigated the transcriptome AS dynamics of T. cruzi (Y strain) infected human foreskin fibroblasts using RNA-Seq data captured over four timepoints (4, 24, 48, and 72 h post infection (hpi)). We identified 1768, 399, 250, and 299 differentially expressed exons (AS exons) at 4, 24, 48, and 72 hpi, respectively, showing that host AS mechanism may have a significant role in the intracellular life cycle of the parasite. We present an exon skipping event in HDAC7, which is a candidate gene that is important in the parasite’s cell cycle. To sum up, this bioinformatics analysis of transcriptome may provide new potential insight into AS regulation in human foreskin fibroblast (HFF) cells infected by T. cruzi and into its implication to the parasite life cycle. Moreover, identified AS genes may provide new potential molecular candidates for improving treatment.

scholarly journals Flagellar Motility ofTrypanosoma cruziEpimastigotes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
G. Ballesteros-Rodea ◽  
M. Santillán ◽  
S. Martínez-Calvillo ◽  
R. Manning-Cela
Keyword(s):  
Life Cycle ◽  
Trypanosoma Cruzi ◽  
Quantitative Description ◽  
Flagellar Motility ◽  
Parasite Life Cycle ◽  
Large Variability ◽  
Rotational Angle ◽  
Ciliary Beating ◽  
Parasite Motility ◽  
Parasite Behavior

The hemoflagellateTrypanosoma cruziis the causative agent of American trypanosomiasis. Despite the importance of motility in the parasite life cycle, little is known aboutT. cruzimotility, and there is no quantitative description of its flagellar beating. Using video microscopy and quantitative vectorial analysis of epimastigote trajectories, we find a forward parasite motility defined by tip-to-base symmetrical flagellar beats. This motion is occasionally interrupted by base-to-tip highly asymmetric beats, which represent the ciliary beat of trypanosomatid flagella. The switch between flagellar and ciliary beating facilitates the parasite's reorientation, which produces a large variability of movement and trajectories that results in different distance ranges traveled by the cells. An analysis of the distance, speed, and rotational angle indicates that epimastigote movement is not completely random, and the phenomenon is highly dependent on the parasite behavior and is characterized by directed and tumbling parasite motion as well as their combination, resulting in the alternation of rectilinear and intricate motility paths.

Temperature, Mitochondria, and Reye's Syndrome

PEDIATRICS ◽  
1983 ◽  
Vol 71 (6) ◽  
pp. 985-985
Author(s):  
RIF S. EL-MALLAKH
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Protozoan Parasite ◽  
Mitochondrial Enzyme ◽  
Reye's Syndrome ◽  
Electron Microscopic ◽  
Microscopic Studies ◽  
Mitochondrial Defect ◽  
Intracellular Protozoan Parasite

To the Editor.— Mitochondrial failure, manifest by changes in mitochondrial enzyme activity1-3 and morphology,4-5 is central to Reye's syndrome (RS).6 Although it has been variously hypothesized that the mitochondrial changes are secondary to an exogenous toxin,7-12 or an intrinsic mitochondrial defect,6 the actual cause remains obscure. Electron microscopic studies have shown sweelling and loss of cristate in mitochondria of patients with RS. It is interesting that very similar changes occur in Trypanosoma cruzi.13-16 T cruzi is an extracellular/intracellular protozoan parasite which causes Chagas' disease.17

scholarly journals In vitro activity of Etanidazole against the protozoan parasite Trypanosoma cruzi

2004 ◽  
Vol 99 (2) ◽  
pp. 233-235 ◽  
Author(s):  
Patricia B Petray ◽  
María J Morilla ◽  
Ricardo S Corral ◽  
Eder L Romero
Keyword(s):  
Trypanosoma Cruzi ◽  
Protozoan Parasite ◽  
Vitro Activity ◽  
In Vitro Activity

scholarly journals Elucidating the Mechanism of Trypanosoma cruzi Acquisition by Triatomine Insects: Evidence from a Large Field Survey of Triatoma infestans

2020 ◽  
Vol 5 (2) ◽  
pp. 87
Author(s):  
Aaron W. Tustin ◽  
Ricardo Castillo-Neyra ◽  
Laura D. Tamayo ◽  
Renzo Salazar ◽  
Katty Borini-Mayorí ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Regression Models ◽  
Control Strategies ◽  
Protozoan Parasite ◽  
Etiologic Agent ◽  
Triatoma Infestans ◽  
Large Field ◽  
Blood Sucking ◽  
Triatomine Bugs ◽  
Cruzi Infection

Blood-sucking triatomine bugs transmit the protozoan parasite Trypanosoma cruzi, the etiologic agent of Chagas disease. We measured the prevalence of T. cruzi infection in 58,519 Triatoma infestans captured in residences in and near Arequipa, Peru. Among bugs from infected colonies, T. cruzi prevalence increased with stage from 12% in second instars to 36% in adults. Regression models demonstrated that the probability of parasite acquisition was roughly the same for each developmental stage. Prevalence increased by 5.9% with each additional stage. We postulate that the probability of acquiring the parasite may be related to the number of feeding events. Transmission of the parasite does not appear to be correlated with the amount of blood ingested during feeding. Similarly, other hypothesized transmission routes such as coprophagy fail to explain the observed pattern of prevalence. Our results could have implications for the feasibility of late-acting control strategies that preferentially kill older insects.

Classification of miRNA-related sequence variations

Epigenomics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 463-481 ◽  
Author(s):  
Karin Hrovatin ◽  
Tanja Kunej
Keyword(s):  
Related Sequence ◽  
Sequence Variations

Recent Progress in Asymmetric Catalysis with Chiral Metal-Organic Frameworks

2020 ◽  
Vol 984 ◽  
pp. 195-204
Author(s):  
Meng Xi Zhang
Keyword(s):  
Asymmetric Catalysis ◽  
Active Sites ◽  
Recent Progress ◽  
Metal Organic Frameworks ◽  
Future Research ◽  
Asymmetric Catalysts ◽  
The Future ◽  
Metal Organic ◽  
Specific Reactions

Chiral metal-organic frameworks (CMOFs) have shown great promises in the applications of asymmetric catalysis with highly enantioselective. Herein, we briefly overview recent processes of MOF-based asymmetric catalysts based on a classification of reaction types. And we mainly focus on the structures and compositions of the active sites in these catalysts and their performances in specific reactions. In addition, some of their important unique features are critically emphasized alongside. Challenges of the future research are discussed also at the end of this review.

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