Publications by authors named "Gabriela de A Burle-Caldas"
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is an illness that affects 6-8 million people worldwide and is responsible for approximately 50,000 deaths per year. Despite intense research efforts on Chagas disease and its causative agent, there is still a lack of effective treatments or strategies for disease control. Although significant progress has been made toward the elucidation of molecular mechanisms involved in host-parasite interactions, particularly immune evasion mechanisms, a deeper understanding of these processes has been hindered by a lack of efficient genetic manipulation protocols.
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- The TcK2 protein kinase of Trypanosoma cruzi is similar to the human kinase PERK and is crucial for the parasite's proliferation in mammalian cells; its absence leads to increased differentiation into infective forms.
- A study confirmed that TcK2-null cells express proteins associated with infective stages and showed decreased phosphorylation of factors that promote growth, resulting in lower proliferation rates.
- Screening of 379 kinase inhibitors identified Dasatinib and PF-477736 as effective inhibitors of TcK2, with Dasatinib showing potential as a therapeutic target for Chagas disease due to its selective efficacy against normal amastigotes but not against TcK2-depleted parasites.
Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi.
PLoS Negl Trop Dis
October 2022
Chagas disease, caused by the protozoan Trypanosoma cruzi, is a serious chronic parasitic disease, currently treated with Nifurtimox (NFX) and Benznidazole (BZ). In addition to high toxicity, these drugs have low healing efficacy, especially in the chronic phase of the disease. The existence of drug-resistant T.
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- Trans-sialidases (TS) are enzymes on the Trypanosoma cruzi parasite, important for its virulence in Chagas disease, and only a few have catalytic activity.
- Researchers used CRISPR-Cas9 to create knockout cell lines lacking active trans-sialidases, finding that these mutants had no TS activity and exhibited impaired development and egress from host cells.
- In experiments with mice, aTS mutants did not cause infection and could even provide immunity against virulent strains, suggesting they could be developed into a vaccine for Chagas disease, which currently has no effective treatment.
Trypanosoma cruzi is a protozoan parasite that causes Chagas disease, an illness that affects 6-7 million people and for which there is no effective drug therapy or vaccine. The publication of its complete genome sequence allowed a rapid advance in molecular studies including in silico screening of genes involved with pathogenicity as well as molecular targets for the development of new diagnostic methods, drug therapies and prophylactic vaccines. Alongside with in silico genomic analyses, methods to study gene function in this parasite such as gene deletion, overexpression, mutant complementation and reporter gene expression have been largely explored.
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