Trypanosoma cruzi Biology, Pathogenesis and Promising Therapeutic Candidates for Intervention

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: 30 April 2024 | Viewed by 2506

Special Issue Editor


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Guest Editor
School of Medicine, The City University of New York, New York, NY 10031, USA
Interests: Chagas disease; host–pathogen interactions; immunity; drug and vaccine discovery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease, or American trypanosomiasis, which is widely spread in Latin America. The pathogenesis of Chagas disease is complicated and multifactorial, and involves many interactive pathways. The current therapy for Chagas disease is limited and unsatisfactory.

Therefore, this Special Issue will focus on recent advances in the biology and molecular pathogenesis of Trypanosoma cruzi infection and promising new therapeutic candidates for Chagas disease and their challenges.

Prof. Dr. Fernando Villalta
Guest Editor

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Keywords

  • Trypanosoma cruzi
  • Chagas disease
  • therapeutic candidates
  • molecular pathogenesis
  • immunity

Published Papers (2 papers)

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Research

24 pages, 5606 KiB  
Article
Implications of Flagellar Attachment Zone Proteins TcGP72 and TcFLA-1BP in Morphology, Proliferation, and Intracellular Dynamics in Trypanosoma cruzi
by Normanda Souza-Melo, Carolina de Lima Alcantara, Juliana Cunha Vidal, Gustavo Miranda Rocha and Wanderley de Souza
Pathogens 2023, 12(11), 1367; https://doi.org/10.3390/pathogens12111367 - 18 Nov 2023
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Abstract
The highly adaptable parasite Trypanosoma cruzi undergoes complex developmental stages to exploit host organisms effectively. Each stage involves the expression of specific proteins and precise intracellular structural organization. These morphological changes depend on key structures that control intracellular components’ growth and redistribution. In [...] Read more.
The highly adaptable parasite Trypanosoma cruzi undergoes complex developmental stages to exploit host organisms effectively. Each stage involves the expression of specific proteins and precise intracellular structural organization. These morphological changes depend on key structures that control intracellular components’ growth and redistribution. In trypanosomatids, the flagellar attachment zone (FAZ) connects the flagellum to the cell body and plays a pivotal role in cell expansion and structural rearrangement. While FAZ proteins are well-studied in other trypanosomatids, there is limited knowledge about specific components, organization, and function in T. cruzi. This study employed the CRISPR/Cas9 system to label endogenous genes and conduct deletions to characterize FAZ-specific proteins during epimastigote cell division and metacyclogenesis. In T. cruzi, these proteins exhibited distinct organization compared to their counterparts in T. brucei. TcGP72 is anchored to the flagellar membrane, while TcFLA-1BP is anchored to the membrane lining the cell body. We identified unique features in the organization and function of the FAZ in T. cruzi compared to other trypanosomatids. Deleting these proteins had varying effects on intracellular structures, cytokinesis, and metacyclogenesis. This study reveals specific variations that directly impact the success of cell division and differentiation of this parasite. Full article
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15 pages, 5807 KiB  
Article
Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease
by Amanda Fortes Francisco, Giovane R. Sousa, Mhairi Vaughan, Harry Langston, Archie Khan, Shiromani Jayawardhana, Martin C. Taylor, Michael D. Lewis and John M. Kelly
Pathogens 2023, 12(11), 1364; https://doi.org/10.3390/pathogens12111364 - 17 Nov 2023
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Abstract
Chronic Chagas cardiomyopathy (CCC) results from infection with the protozoan parasite Trypanosoma cruzi and is a prevalent cause of heart disease in endemic countries. We previously found that cardiac fibrosis can vary widely in C3H/HeN mice chronically infected with T. cruzi JR strain, [...] Read more.
Chronic Chagas cardiomyopathy (CCC) results from infection with the protozoan parasite Trypanosoma cruzi and is a prevalent cause of heart disease in endemic countries. We previously found that cardiac fibrosis can vary widely in C3H/HeN mice chronically infected with T. cruzi JR strain, mirroring the spectrum of heart disease in humans. In this study, we examined functional cardiac abnormalities in this host:parasite combination to determine its potential as an experimental model for CCC. We utilised electrocardiography (ECG) to monitor T. cruzi-infected mice and determine whether ECG markers could be correlated with cardiac function abnormalities. We found that the C3H/HeN:JR combination frequently displayed early onset CCC indicators, such as sinus bradycardia and right bundle branch block, as well as prolonged PQ, PR, RR, ST, and QT intervals in the acute stage. Our model exhibited high levels of cardiac inflammation and enhanced iNOS expression in the acute stage, but denervation did not appear to have a role in pathology. These results demonstrate the potential of the C3H/HeN:JR host:parasite combination as a model for CCC that could be used for screening new compounds targeted at cardiac remodelling and for examining the potential of antiparasitic drugs to prevent or alleviate CCC development and progression. Full article
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