| Texto completo | |
| Autor(es): |
Saenz-Garcia, Jose Luis
;
Souza-Melo, Normanda
;
Miranda, Juliana Severo
;
Borges, Beatriz
;
Pacheco-Lugo, Lisandro A.
;
Quintero-Solano, Jose M.
;
Moretti, Nilmar
;
Wheeler, Richard
;
Soares-Medeiros, Lia C.
;
DaRocha, Wanderson D.
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PATHOGENS; v. 14, n. 4, p. 17-pg., 2025-03-25. |
| Resumo | |
Chagas disease, caused by Trypanosoma cruzi, is a neglected tropical disease with few options for treatment and no available vaccine. Deletion mutants for live attenuated vaccines, particularly deletions of proteins related to the cytoskeleton, have been widely tested in related parasites but candidates have not been tested in T. cruzi. Kharon is one such protein, identified as being associated with the cytoskeleton in Leishmania and essential for amastigote replication. Here we investigated the T. cruzi Kharon ortholog (TcKharon) to test if it has orthologous function and thus potential in generating a live attenuated vaccine. In silico analysis predicted TcKharon to be an intrinsically disordered protein, consistent with its ortholog feature, and GFP fusion protein revealed that TcKharon is associated with the cytoskeleton of epimastigotes. CRISPR-Cas9-mediated gene disruption impaired epimastigote proliferation and cytokinesis, resulting in altered nucleus-to-kinetoplast ratios and pronounced morphological defects, particularly in the posterior cell region. Despite these abnormalities, TcKharon-/- mutants retained the ability to differentiate into metacyclic trypomastigotes and exhibited in vitro infection rates comparable to wild-type parasites. Our data show that TcKharon is crucial for cell morphology. However, in contrast to close related parasites, TcKharon is not essential for in vitro infectivity. (AU) | |
| Processo FAPESP: | 20/07870-4 - Mecanismos de adaptação de tripanossomatídeos ao hospedeiro através de controle da transcrição, síntese proteica e secreção de vesículas extracelulares |
| Beneficiário: | Ana Claudia Trocoli Torrecilhas |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 18/09948-0 - Estudo da acetilação proteica em Leishmania |
| Beneficiário: | Nilmar Silvio Moretti |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 22/03075-0 - Desvendando os mecanismos regulatórios envolvidos na relação parasito hospedeiro da Leishmania: foco nas alterações pós-transcricionais e pós-traducionais |
| Beneficiário: | Nilmar Silvio Moretti |
| Modalidade de apoio: | Auxílio à Pesquisa - Projeto Inicial |