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http://hdl.handle.net/1843/62488| Type: | Artigo de Periódico |
| Title: | Disruption of Active Trans-Sialidase Genes Impairs Egress from Mammalian Host Cells and Generates Highly Attenuated Trypanosoma cruzi Parasites |
| Authors: | Gabriela de A. Burle-Caldas Júlia T. de Castro Nailma Aprigio Dos Santos Viviane Grazielle da Silva Fernanda L. B. Mugge Sergio Schenkman Ricardo T. Gazzinelli Santuza Maria Ribeiro Teixeira Antônio Edson R. Oliveira Milton C. A. Pereira João Luís Reis-Cunha Anderson Coqueiro dos Santos Dawidson Assis Gomes Daniella C. Bartholomeu Nilmar S. Moretti |
| Abstract: | Trans-sialidases (TS) are unusual enzymes present on the surface of Trypanosoma cruzi, the causative agent of Chagas disease. Encoded by the largest gene family in the T. cruzi genome, only few members of the TS family have catalytic activity. Active trans-sialidases (aTS) are responsible for transferring sialic acid from host glycoconjugates to mucins, also present on the parasite surface. The existence of several copies of TS genes has impaired the use of reverse genetics to study this highly polymorphic gene family. Using CRISPR-Cas9, we generated aTS knockout cell lines displaying undetectable levels of TS activity, as shown by sialylation assays and labeling with antibodies that recognize sialic acid-containing mucins. In vitro infection assays showed that disruption of aTS genes does not affect the parasite’s capacity to invade cells or to escape from the parasitophorous vacuole but resulted in impaired differentiation of amastigotes into trypomastigotes and parasite egress from the cell. When inoculated into mice, aTS mutants were unable to establish infection even in the highly susceptible gamma interferon (IFN-γ) knockout mice. Mice immunized with aTS mutants were fully protected against a challenge infection with the virulent T. cruzi Y strain. Altogether, our results confirmed the role of aTS as a T. cruzi virulence factor and indicated that aTS play a major role during the late stages of intracellular development and parasite egress. Notably, mutants lacking TS activity are completely avirulent in animal models of infection and may be used as a live attenuated vaccine against Chagas disease. |
| Subject: | Trypanosoma cruzi Vacinas Virulência |
| language: | eng |
| metadata.dc.publisher.country: | Brasil |
| Publisher: | Universidade Federal de Minas Gerais |
| Publisher Initials: | UFMG |
| metadata.dc.publisher.department: | ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA ICB - DEPARTAMENTO DE PARASITOLOGIA ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS |
| Rights: | Acesso Aberto |
| metadata.dc.identifier.doi: | https://doi.org/10.1128/mbio.03478-21 |
| URI: | http://hdl.handle.net/1843/62488 |
| Issue Date: | 25-Jan-2022 |
| metadata.dc.url.externa: | https://journals.asm.org/doi/10.1128/mbio.03478-21 |
| metadata.dc.relation.ispartof: | Microbial Genetics |
| Appears in Collections: | Artigo de Periódico |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Disruption of Active Trans-Sialidase Genes Impairs Egress from Mammalian Host Cells and Generates Highly Attenuated Trypanosoma cruzi Parasites.pdf | 3.2 MB | Adobe PDF | View/Open |
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