Disruption of Active Trans-Sialidase Genes Impairs Egress from Mammalian Host Cells and Generates Highly Attenuated Trypanosoma cruzi Parasites

Página do item simplificado
dc.creatorGabriela de A. Burle-Caldas
dc.creatorJúlia T. de Castro
dc.creatorNailma Aprigio Dos Santos
dc.creatorViviane Grazielle da Silva
dc.creatorFernanda L. B. Mugge
dc.creatorSergio Schenkman
dc.creatorRicardo T. Gazzinelli
dc.creatorSantuza Maria Ribeiro Teixeira
dc.creatorAntônio Edson R. Oliveira
dc.creatorMilton C. A. Pereira
dc.creatorJoão Luís Reis-Cunha
dc.creatorAnderson Coqueiro dos Santos
dc.creatorDawidson Assis Gomes
dc.creatorDaniella C. Bartholomeu
dc.creatorNilmar S. Moretti
dc.date.accessioned2024-01-08T20:00:06Z
dc.date.accessioned2025-09-09T01:32:02Z
dc.date.available2024-01-08T20:00:06Z
dc.date.issued2022-01-25
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1128/mbio.03478-21
dc.identifier.issn2150-7511
dc.identifier.urihttps://hdl.handle.net/1843/62488
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofMicrobial Genetics
dc.rightsAcesso Aberto
dc.subjectTrypanosoma cruzi
dc.subjectVacinas
dc.subjectVirulência
dc.subject.otherTrypanosoma cruzi
dc.subject.otherTrans-sialidase
dc.subject.otherVirulence
dc.subject.otherVaccine
dc.subject.otherCRISPR-Cas9
dc.titleDisruption of Active Trans-Sialidase Genes Impairs Egress from Mammalian Host Cells and Generates Highly Attenuated Trypanosoma cruzi Parasites
dc.typeArtigo de periódico
local.citation.epage17
local.citation.issue1
local.citation.spagee03478-21
local.citation.volume13
local.description.resumoTrans-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.
local.identifier.orcidhttps://orcid.org/0000-0002-2588-2842
local.identifier.orcidhttps://orcid.org/0000-0002-9493-1740
local.publisher.countryBrasil
local.publisher.departmentICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA
local.publisher.departmentICB - DEPARTAMENTO DE PARASITOLOGIA
local.publisher.departmentICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS
local.publisher.initialsUFMG
local.url.externahttps://journals.asm.org/doi/10.1128/mbio.03478-21

Arquivos

Pacote original

Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
Disruption of Active Trans-Sialidase Genes Impairs Egress from Mammalian Host Cells and Generates Highly Attenuated Trypanosoma cruzi Parasites.pdf
Tamanho:
3.13 MB
Formato:
Adobe Portable Document Format
Baixar

Licença do pacote

Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
License.txt
Tamanho:
1.99 KB
Formato:
Plain Text
Descrição:
Baixar

Coleções

Artigo de Periódico

Logo UFMG